Prize4Life Blog

Regenerative Medicine and Cell Therapy Briefing: The Road to Commercialization

noreply@blogger.com (Nate) — Thu, 27 Oct 2011 18:48:00 +0000

The following blog was originally posted on Prize4Life's ALS Forum. For more articles on the latest research and drug development news, along with a wide variety of ALS research tools and resources, visit ResearchALS.org.

Amidst the buzz of partnering activity throughout the three day BioPharm America 2011 meeting held in Boston, MA from September 7-9, 2011, there were ample opportunities to hear industry leaders' perspectives on industry trends through workshops and panel discussions. Of particular interest was a session focused on stem cells in regenerative medicine and featured here, given the powerful allure of stem cells to captivate ALS researchers, drug developers, and patients alike. With the generation of ALS patient-derived iPS cell lines and the ground-breaking safety trial of Neuralstem's stem cell therapy in ALS patients, there are high expectations for stem cells to revolutionize ALS drug discovery and therapeutics. Let's hear what industry leaders had to say ...

The session opened with a panel moderated by Brock Reeve, Executive Director of the Harvard Stem Cell Institute. In his introductory comments, Reeve reminded the audience that the first iPS publication came out just five years ago and since then the technology has become almost commonplace in labs across the world. Moreover, the technology has already been improved upon: a subsequent technique was developed to directly induce differentiated fibroblasts into a motor neuron identity, skipping the reprogramming step to the undifferentiated state. These so called induced motor neurons (or iMN) could potentially make it even easier and faster to generate patient specific models of motor neuron disease. [See also related news on recent advances to purify and differentiate stem cells as well as remaining potential pitfalls.]

The "big opportunity" that lay in stem cells was clearly appreciated by the pharma and biotech panel experts who acknowledged the growing trend to incorporate adult, embryonic or induced pluripotent stem cell technologies into a variety of efforts, ranging from drug discovery to development of cell-based therapies. The exciting ferment in the stem cell space has also added to industry's growing interest in and enthusiasm for fostering academic collaborations. While innovation in the stem cell space can come from anywhere, Gary Neil, Corporate VP at J&J, expects most to come from the academic sector.

Both panelists and audience members commented on the more frequent appearances of pharma representative of the likes of Pfizer, J&J, and GSK turning up at regenerative medicine conferences and partnering meetings such as this one as illustrative of pharma's growing interest in regenerative medicine. One explicit example of this interest, Shire's recent acquisition of AdvBioHealing, was taken as a signal that the specialty pharma's intends to build a regenerative medicine franchise around its newly acquired iPS technology.

Reeve asked panelist to offer their perspectives on potential breakthroughs within the proximate five-year horizon for regenerative medicine. Near term success was expected for macular degeneration and other eye diseases as well as for diabetes. Simple models with easy to measure clinical endpoints were perceived as more likely to succeed, whereas diseases with more complex biology (i.e.: stroke and ALS) were perceived as more difficult.

The second panel moderated by John McNeish, Founder of Boston Stem Cell and ex-Pfizer Executive Director of Regenerative Medicine, explored the use of stem cells for drug discovery and translation in greater depth. iPS cells in particular hold great excitement for use in disease modeling, target validation, and drug and biomarker discovery programs. iPS cells also offer a unique opportunity to identify which patients are more likely to respond to a drug by first testing the drug on the patient's own stem cells. In contrast to the relatively young iPS field, panelists noted that the more mature areas of adult and embryonic stem cell biology have yielded several cellular therapies that have moved steadily ahead into a clinical setting, including Advanced Cell Technology's hESC-based Retinal Pigment Epithelial (RPE) therapy for degenerative retinal diseases, Geron's hESC-derived oligodendrocyte progenitor cell therapy for spinal cord injury, Neuralstem's neural stem cell therapy for ALS and major depression, and over 37 ongoing clinical trials using adult stem cell therapeutics.

How close are we to remediating disease in a dish? Very close, according to Leonard Zon, stem cell researcher at HHMI/Children's Hospital Boston and co-founder of Fate Therapeutics, who projects that in three to five years researchers will be able to successfully treat a disease pathology exhibited by the affected cell type derived from patient iPS cells. This is an area of intense investigation, as many groups are actively working to establish disease models in a dish from patient-derived iPS cells and to develop functional assays to enable drug screening, including those studying ALS at The New York Stem Cell Foundation, the California Institute for Regenerative Medicine and elsewhere.

For ALS, progress has been slowed by an unanticipated finding. Unlike motor neurons derived from ALS mouse ESCs, which exhibit a characteristic disease pathology, motor neurons generated from both familial and sporadic ALS patient iPS cell lines lack an obvious disease phenotype even after extended periods in culture. The apparently healthy nature of these cells may bode well for transplantation back into the patient for use as a cellular therapy. However, the difficulty in detecting a disease phenotype necessitates the development of sensitive assays to identify a disease signature, a necessary step before these cells can be used to screen drugs.

While progress is being made on several fronts to advance stem cell-based drug discovery and therapies, the field continues to wrestle with the hype surrounding stem cells - a double edged sword for the field. While a certain amount of hype attracts investment money, it also preys on the vulnerabilities of patient communities, desperate for treatment. As ACT's Business Development Director Matthew Vincent noted, regenerative medicine's snake oil practitioners will hamper legitimate scientific efforts and slow the entire field. He cautioned against getting caught up in the hype and hubris over the revolutionary nature of stem cells when it comes to managing the associated risks, which range from regulatory to manufacturing to reimbursement. Goeff MacKay, President and CEO of Organogenesis, further emphasized the importance of assessing reimbursement very early in the process, calling it an early go/no-go decision point.

To watch the videos of the regenerative medicine panels presented here, click the links: panel 1 and panel 2. Additional meeting coverage discussing pharma trends can be found here: The future of drug development, Angus Russell: Pharma must change to compete in new world market and Creativity, productivity and the future of pharma.

- Sheila Menzies, PhD, Scientific Program Officer at Prize4Life

Dr. Ed Kaye on ALS and Incentive Prizes: The Extended Interview

noreply@blogger.com (Nate) — Tue, 25 Oct 2011 19:36:00 +0000

As part of our continuing series featuring interviews with some of the leading players in the field of ALS research, drug development, and treatment, Prize4Life spoke with Dr. Ed Kaye, currently the Chief Medical Officer at AVI BioPharma and the former Group Vice President and Therapeutic Head for Lysosomal Storage Disorders and Neurodegenerative Diseases at Genzyme Corporation. Dr. Kaye serves on Prize4Life's Scientific Advisory Board. In this video, he shares his thoughts on the recent $1M ALS Biomarker Prize award, the importance of private funding to complement public funding of ALS research, and the potential of the incentive prize model in biomedical research.

You can watch all of the extended interviews by subscribing to our YouTube channel here. You can also view the original video these interviews were collected for, 'Driving Breakthroughs in ALS Research: Prize4Life and the $1M ALS Biomarker Prize,' below.

Dr. Robert Horvitz on ALS Research: The Extended Interview

noreply@blogger.com (Nate) — Fri, 14 Oct 2011 16:53:00 +0000

Earlier this year, Prize4Life interviewed some of the top minds in the ALS research, clinical, and industry communities asking for their thoughts on ALS, the drug development landscape, and the potential of the incentive prize model in spurring biomedical innovation. These interviews were compiled into a short video that was screened at a gala in New York City celebrating the awarding of the $1M ALS Biomarker Prize to Dr. Seward Rutkove.

We are sharing the extended versions of these interviews on our website. The first video featured Dr. Vicki Sato, a professor at Harvard Business School and former president of Vertex Pharmaceuticals. You can view that video here.

The following is an interview with Dr. Robert Horvitz, a Professor of Biology at the Massachusetts Institute of Technology, an investigator with the Howard Hughes Medical Institute, and winner of the 2002 Nobel Prize in Physiology for discovering and characterizing the genes controlling cell death in the nematode worm Caenorhabditis elegans. Dr. Horvitz discusses his personal connection with ALS, the need for increased funding in the field, and how his work advances ALS research.

You can also view the original video, 'Driving Breakthroughs in ALS Research: Prize4Life and the $1M ALS Biomarker Prize,' below.

5K4Life Is Fast Approaching!

noreply@blogger.com (Nate) — Tue, 11 Oct 2011 19:07:00 +0000

The Third Annual 5K4Life, benefiting Prize4Life, is almost upon us!

Our founder and CEO, Avi Kremer, will be in attendance for the race this year. Avi was diagnosed with ALS in 2006 and launched Prize4Life to rapidly accelerate the discovery of a cure for the disease.

What: Third Annual 5K4Life Road Race

When: November 6th

8:00 - 10:45 AM Race Registration and Race Packet Pick-Up

11:00 AM Race Start

Where: Kendall Square / 15 Cambridge Center

Lawn at the bend of Galileo Galilei Way and Binney Street

Members of Team Ashley helped make last year's 5K4Life a tremendous success...

ALS is a devastating neurodegenerative disease that afflicts more than 600,000 people around the world, robbing them of the ability to move, speak, and ultimately to breathe. Most patients will die within 2 to 5 years.

But you can be a part of the cure! Support Prize4Life's efforts to drive breakthroughs in research at the 5K4Life!

Here's how you can help:

1. Register today for the 5K at www.5k4life.org

2. Volunteer for the race by emailing events@prize4life.org

3. Donate to Prize4Life here

4. Fundraise for the 5K4Life to help bring us closer to a world free of ALS

Fundraising for Prize4Life is a way to honor someone you know living with ALS, to remember someone who has passed away from the disease, or to deliver hope to the thousands of ALS patients and their families battling it. Join Prize4Life's efforts, and the next ALS breakthrough could be yours...

Create your own fundraising page here.

Thank you for your support! Please share word of the 5K4Life with your friends and networks, and RSVP for the race on Facebook.

"Trapped" Can Now Be Viewed Online!

noreply@blogger.com (Nate) — Thu, 08 Sep 2011 17:18:00 +0000

In April of 2009, a group of filmmakers came together to create "Trapped," a short film meant to raise awareness of ALS and marshal support for efforts to discover a cure. Director/Producer James Takata, Writers/Producers Zach Lewis and Jim Mahoney, and Producer Jhennifer Webberley worked with Amy Yamner Jenkins, the Chair of Prize4Life's Board of Directors, on the project. The film tells the story of Stephen, a talented young composer and pianist who discovers he has ALS after an eerie progression of symptoms. And though he begins to lose his ability to physically write music and play the piano, his spirit and genius cannot be taken by the disease. As Director Takata describes, though is body is deteriorating, "his ability is still there."

"Trapped" has been shown at numerous festivals, including the California Independent Film Festival, Methodfest, and the Neuro Film Festival sponsored by the American Academy of Neurology Foundation. The film won a bronze medal at the New York-based Telly Awards.

In 2009, Prize4Life had the opportunity to sit down with some of the creators of the film. You can read a transcript of that interview on our blog here.

For more information on the film's cast and crew, visit the IMDB profile page here.

Mice in Space: The Effects of Low Gravity on Muscle and Bone Degeneration

noreply@blogger.com (Nate) — Mon, 22 Aug 2011 16:23:00 +0000

On July 21, 2011, the American space shuttle program came to an official end when shuttle Atlantis rolled to a stop at NASA’s Kennedy Space Center on Merritt Island in Florida. For 30 years, the shuttle program ferried astronauts into Earth’s orbit to launch, repair, and recover satellites, construct the International Space station, and conduct countless experiments and invaluable scientific research.

One such experiment, undertaken during the final shuttle mission, studied the loss of bone and muscle mass in a micro-gravity environment as well as a therapy that might be able to arrest that degeneration. Mary Bouxsein, PhD, a scientist in Beth Israel Deaconess Medical Center’s (BIDMC) department of Advanced Orthopedic Studies and Assistant Professor of Orthopedic Surgery at Harvard Medical School, served as the co-principal investigator of the study, leading a team of researchers from BIDMC, Amgen, BioServe Space Technologies, and the University of North Carolina. The study was funded by NASA’s Ames Research Center.

The research will not only yield insights into how astronauts can address a fundamental problem of long space flights, it could also lead to a greater understanding and potential prevention of bone loss for aging or diseased individuals here on Earth.

“Mechanical loading is required to maintain musculoskeletal health,” explains Dr. Bouxsein. “On earth, our bones experience mechanical forces from being pushed and pulled by muscles that work against gravity to keep us upright and moving around, as well as from the impact of our body weight against the ground. These forces are much lower in micro-gravity environments and, as a result, the rate of bone loss among astronauts is about 10 times greater than that seen in postmenopausal women. So, while this research is designed to better understand and prevent skeletal fragility among astronauts, it may also tell us a great deal about the future potential of this novel therapy to improve bone strength here on earth, in both older persons and in individuals with reduced physical activity due to various clinical conditions, such as stroke, spinal cord injury or cerebral palsy.”

You can watch Dr. Bouxsein explain her team’s work leading up to the shuttle launch in the video below.

Thirty mice (affectionately dubbed ‘mousetronauts’) were launched into space as a part of mission STS-135, the final shuttle flight. Dr. Bouxsein’s rather enthusiastic blog details the mission from soup to nuts (or launch to post-touchdown beach party after all of the equipment, supplies, and specimens had been collected at the Kennedy Space Center). You can read her blog here.

One of Dr. Bouxsein’s collaborators was Dr. Seward Rutkove, also of Beth Israel Deaconess Medical Center. Dr. Rutkove is the Chief of the Division of Neuromuscular Diseases at BIDMC as well as the recipient of Prize4Life’s $1M ALS Biomarker Prize.

Dr. Rutkove’s lab will be conducting studies over the next six months on the two specimens they received from the experiment in order to learn more about the progression of muscle atrophy that accompanies disuse. Rutkove is the developer of electrical impedance myography (the work for which he won our million-dollar prize), a process which compares the flow of an electrical current through healthy muscle and muscle that has degenerated as ALS progresses. You can read more about EIM technology in an earlier blog post here.

There is currently no reliable diagnostic test for ALS. However, by making a distinction between the muscle degeneration that occurs due to illness or lack of use (accentuated in this experiment by the micro-gravity of a low Earth orbit) and atrophy that stems from a neurogenic disorder, electrodiagnostic tests might be able to tell scientists more about the nature of ALS in a given patient sooner which could improve the impact of potential therapies.

Out With The Old And In with the … Old: The Drug Repositioning Conference

noreply@blogger.com (Nate) — Fri, 19 Aug 2011 16:02:00 +0000

"One of the things you learn from years of dealing with drug people, is that you can turn your back on a person, but never turn your back on a drug."

- Raoul Duke, Fear and Loathing in Las Vegas

"In the field of observation, chance favors only the prepared mind."

- Louis Pasteur

The above quotes allude to the growing realization that new opportunities exist for many "old" drugs, but sophisticated knowledge management platforms will be needed to properly identify these drug repositioning opportunities.

Amid the "fear and loathing" accompanying the numerous reports of the drug development pipeline drying-up, the biopharmaceutical industry is warmly embracing the drug repositioning model as an efficient and expedited mechanism to fuel their clinical development programs with "old" drugs that have newly appreciated indications. At the recent Drug Repositioning Conference held in San Francisco, CA on July 13-14, 2011, industry experts convened to share their insights from their own drug repositioning experiences, to discuss the impact drug repositioning has had on the drug development landscape, and to assess new directions for the field.

The concept of drug repositioning (or repurposing) is not new. In the past, serendipitous observations played a principle role in identifying novel uses for approved drugs already on the market for other indications, noted Pankaj Agarwal, Director of Computational Biology, Molecular Discovery & Development at GlaxoSmithKline. Aspirin serves as a classic example.

What is new however is that biopharmas, including Merck Serono, AstraZeneca and GSK, all of whom were represented at this conference, are now placing a premium on leveraging their prior research and development (R&D) investments to rescue stalled clinical-stage compounds by re-investigating their efficacy for treating alternative new indications.

Given the high attrition rate of experimental drugs, drug repositioning offers a "solution for speedy re-introduction of compounds back into the pipeline," commented Natalia Novac, Associate Manager, R&D Knowledge Management Operational Excellence at Merck Serono. While Novac commented that Serono's original repurposing business model had focused on Phase 3 clinical compounds, they now realize that they need to start earlier, after a drug passes Phase I safety and toxicity testing, to plan for secondary indications. Others in the audience advocated preparing even earlier, at the preclinical stage in the product lifecycle, a practice adopted at Pfizer, to identify potential alternative indications that could be used either as a back-up, if efficacy testing for the primary indication fails, or as a repositioning strategy.

Some in the audience challenged the notion that only drugs that have passed Phase I harbor future value for repurposed use, indicating that a drug that failed its initial Phase I study when delivered at a high dose could be safely delivered at a much lower dose that fell within the therapeutic window for the treatment of an alternative indication. Taken together, these divergent criteria argue the utility of broadening eligibility to include all clinical compounds (and perhaps even preclinical compounds) under consideration for repositioning.

Knowledge Management: Pillar of the Drug Repurposing Approach

Nowadays, biopharma is not leaving these hidden, yet potentially golden, repositioning opportunities up to chance alone. There is a concerted effort within biopharma to capture and organize the vast amounts of existing public and proprietary data into rich knowledge networks of biological pathways and disease targets.

Merck Serono, AstraZeneca, and GSK are all heavily investing in various Knowledge Management platforms. Speakers mentioned a host of existing automated technology platforms that review texts (i.e.: publications, abstracts, clinical case reports, etc.), extract entities (i.e.: proteins X and Y) and build relationships between entities (i.e.: protein X activates protein Y) to create biological knowledge networks. These networks could be overlaid onto disease specific network maps to facilitate identification of key, possibly novel, disease targets. This type of approach could also be used to identify the relevant indication(s) based on their drug's established mechanism of action.

In addition to fully automated platforms, organizations such as Thomas Reuters offer MetaMiner Partnerships to "bring the highly specialized expertise in manual curation and disease map development to create new pathways quickly" for its clients. In a collaborative move, Reuters launched a new consortium in July 2011 to map the bioprocesses for all FDA drugs approved in the last three years.

Spotlight on AstraZeneca's High-Investment Foray into Drug Repurposing

AstraZeneca's aptly named New Opportunities group has been tasked with finding new opportunities for existing compounds in areas that the company is currently not working in. Regenerative medicine is one such new area, remarked Nick Brown, Associate Director of Informatics for AstraZeneca's New Opportunities group. Orphan diseases were also considered attractive gateway indications, suggesting that ALS could be within AstraZeneca's sights if the right opportunity were to be identified.

AstraZeneca is going further than most when building their Knowledge Management Platforms. As Brown explained, his group is in the process of bringing together over 2000 proprietary internal databases from across AstraZeneca's global reach. He admittedly faces a huge standardization challenge, but makes the point that these disparate databases contain tons of valuable proprietary information about their own drugs that remain relatively inaccessible. Brown strongly believes that re-capturing this propriety information "hidden away" will reveal novel and lucrative repurposing opportunities for AstraZeneca. Brown has also developed a rich Asset Repositioning Matrix that has already led to the identification of new disease targets and indications, as well as, potential collaborators and key opinion leaders.

The 20-member group functions as a virtual R&D with a budget comparable to one of AstraZeneca's therapeutic areas, underscoring their confidence in and commitment to the repurposing strategy. Formation and funding of this group also emphasizes AstraZeneca's belief, also expressed frequently by other conference attendees, that factoring human data into the knowledge maps is "huge". Given the size of AstraZeneca's investment and commitment it was interesting that the primary focus to date for this group had been on late stage Phase II or III compounds in clinical development, suggesting that a considerable amount of Phase I and pre-clinical information still remained untapped.

The value proposition behind the drug repositioning approach is obvious: generate new revenue streams by leveraging prior capital- and resource-intensive investments and in so doing offer patients better treatments. While the opportunities are vast, there are several important limitations, including issues of commercialization, patentability, freedom of use, and the regulatory path to approval, to name just a few. Not to fear - speakers including commercialization expert David Cavalla, regulatory expert Ken Phelps, and patent attorney Kevin McLaren, discussed a slew of strategies to work through these vital issues. Further discussion of these issues can be found here and here.

So given the buzz generated at this conference, my question is: can ALS drug development benefit from a drug repositioning approach?

One way I thought about this was in terms of speed. The critical need for expedited drug development for ALS is underscored by the aggressive and merciless progression of disease resulting in death typically within three years after diagnosis. Clinical development of a repurposed drug could significantly shorten the traditional drug development timeline and bring an efficacious drug to patients faster and, in so doing, offer access to more ALS patients.

Ok, so yes, repositioning saves time, but is it relevant to ALS? As noted by speaker Chris Lipinski, Scientific Advisor at Melior Discovery, 30% of clinical compounds have new uses and (strikingly) 90% of these new uses are on-target. These findings indicate that rather than finding new molecular targets for old drugs, we are discovering the relevance of these druggable targets in new indications, implying that there are major gaps and flaws in our fundamental understanding of disease biology.

Final thought: As our understanding of ALS biology deepens and disease targets are further validated, a drug repurposing approach could be a valuable complement to traditional ALS drug discovery efforts.

So who's with me?

- Sheila Menzies, Scientific Program Officer at Prize4Life

This blog post was originally published on the ALS Forum at www.researchALS.org.

Dr. Vicki Sato on Prize4Life: The Extended Interview

noreply@blogger.com (Nate) — Wed, 10 Aug 2011 16:41:00 +0000

In June of 2011, Prize4Life formally celebrated the awarding of the $1M ALS Biomarker Prize to Dr. Seward Rutkove for his development of eletrical impedance myography (EIM), a tool that has the potential to radically accelerate the development of drugs for ALS. To mark that occasion, Prize4Life interviewed some of the top minds in the ALS research, clinical, and industry communities asking for their thoughts on ALS, the drug development landscape, and the potential of the incentive prize model in spurring biomedical innovation. These interviews were compiled into a short video screened at our award gala.

Over the course of this summer, Prize4Life will be releasing extended versions of those interviews on our website and social media channels. The first is an interview with Dr. Vicki Sato, a Professor of Management Practice at Harvard Business School, a Professor of the Practice in the Department of Molecular and Cell Biology at Harvard University, a business advisor to Atlas Ventures, the former President of Vertex Pharmaceuticals, and a current member of Prize4Life's Board of Directors.

You can also view the original video, 'Driving Breakthroughs in ALS Research: Prize4Life and the $1M ALS Biomarker Prize,' below.

Stay tuned for additional interviews to be released at www.blog.prize4life.org, or follow along on our Facebook page or our YouTube channel.

Biogen Idec/Knopp Biosciences Dexpramipexole Trial

noreply@blogger.com (Nate) — Fri, 10 Jun 2011 15:04:00 +0000

In early April, Knopp Biosciences and Biogen Idec announced the enrollment of the first patient into a Phase III clinical trial of the experimental drug dexpramipexole, a novel treatment to extend the lives of individuals with ALS. It is an exciting development for the field, and we wanted to highlight some of the details and history of the drug for the blog.

The trial will enroll 804 patients who will be followed for 12-18 months. Half of this group will receive two doses per day of a 150mg oral tablet of the drug; the other half will receive a similarly dosed placebo.

In order to participate in the trial, patients must:

Be 18 to 80 years old.
Have a diagnosis of familial or sporadic ALS.
Have experienced symptom onset within 24 months prior to beginning the trial.
Meet World Federation of Neurology El Escorial criteria for a “possible,” “laboratory-supported probable,” “probable” or “definite” ALS diagnosis.
Have lung function of 65 percent or more at screening, measured by a test called the upright slow vital capacity (SVC).
Be able to swallow tablets at the time of study entry.

Participants must not:

Have any other medically significant illness.
Have any clinically significant abnormal laboratory values.
Be pregnant or breastfeeding.
Have prior exposure to dexpramipexole.
Be currently taking pramipexole or other dopamine agonists.

The trial will be enrolling patients at 83 locations in 28 states and 10 countries (Australia, Canada, and several European countries). For more detailed enrollment information as well a list of study locations, visit the listing for the Phase III dexpramipexole trial at ClinicalTrials.gov. It should be noted that most sites have yet to start recruiting as of the publication of this post. Contact information for individual sites can be found at ClinicalTrials.gov, and the Medical Director of the study at Biogen can be reached at ALSclinicaltrials@biogenidec.com.

A brief history of dexpramipexole:

Early 2000’s – Dexpramipexole is first identified as a potential ALS therapy by Dr. James Bennett of the University of Virginia and first preliminary academic clinical studies are conducted using Dex to treat ALS patients.

2007 – Knopp Biosciences completes a formal Phase I trial of dexpramipexole that demonstrates the drug is safe and well-tolerated among healthy volunteers.

2009 – Results from a Phase II study of the drug again demonstrate safety and show a ‘dose-dependent trend in slowing the rate of disease progression’ in the first part of the study and a ‘trend toward a survival benefit’ among the highest-dosed patients in the second part of the study. Drug receives ‘fast-track’ designation from the US FDA.

2010 – Knopp Biosciences and Biogen Idec enter into an exclusive, worldwide license agreement to develop and commercialize dexpramipexole.

2011 – Knopp Biosciences and Biogen Idec enroll first patient in Phase III clinical trial of dexpramipexole.

So what is the expected benefit of dexpramipexole (colloquially known as dex)?

According to Michael Bozik, a neurologist and the President and CEO of Knopp Biosciences, “If we confirm in larger studies what we saw in earlier studies, we believe it has the promise to extend life [up to six months or more].”

Riluzole, the only currently available drug for ALS, extends life by about 2-3 months. Patients who are currently taking Riluzole are not disqualified from participating in the Phase III trial, though they must either have been taking a stable dose of the drug for at least 60 days or have discontinued the drug for at least 30 days.

Though the launch of this trial is an encouraging development, there are still several hurdles that must be cleared. The Phase III trial will enroll eight times the number of patients as previous Dex trials and will need to exceed the relatively ‘modest’ effect demonstrated in the Phase II trial. Additionally, the mechanism behind the drug is not well understood. According to Dr. Bozik, Knopp is still researching the underlying function of the drug in collaboration with Yale University. Finally, even if the trial demonstrates efficacy, the earliest an application for FDA approval could be submitted is 2013—assuming the study is completed on time (estimated end date of February 2013) and the FDA does not require a second round of Phase III trials.

Nevertheless, dexpramipexole provides cause for hope for the thousands of patients and families battling this disease. We will continue to closely follow and report on any developments related to this drug.

Prizes 101: An Introduction to Prizes for Global Health Innovation on World TB Day

noreply@blogger.com (Nate) — Thu, 24 Mar 2011 17:00:00 +0000

A guest blog post from our colleagues at Results for Development:

World TB Day, which falls on March 24 every year, marks Dr. Robert Koch's discovery of Mycobacteriumtuberculosis, the bacteria that cause tuberculosis (TB). Dr. Koch's discovery was a remarkable step forward in diagnosing, treating and fighting the TB epidemic, which takes over two million lives every year around the world. Despite the global interest in curbing the TB epidemic, the technology to diagnose the disease in most developing countries has not been updated for the last 125 years. Prizes could pave the way to develop a new and improved TB diagnostic.

Paul Wilson and Amrita Palriwala of Results for Development Institute (R4D) have studied the potential of prizes to spur the development of new health technologies, such as drugs, vaccines, diagnostics and medical devices, in the developing world. They spoke to their colleague Gina Lagomarsino about their forthcoming report “Prizes for Global Health Technologies,” which will be released next Tuesday, March 29th on R4D’s Center for Global Health R&D Policy Assessment website.

Gina: Why did you focus on prizes for diagnostics, as opposed to vaccines or drugs? Why TB diagnostics in particular?

Amrita: Our Center’s mission is to provide an evidence base for supporting ideas to advance technologies for neglected diseases. As we landscaped proposals, we found that proposals for prizes for new TB tests were among the most developed. Yet although prize competitions are well known in mathematics and other sciences, there is little experience using prizes to drive innovation in biomedicine. This lack of knowledge around how prizes work for health product development and global health in particular was the impetus for this work.

In general, diagnostics are a good testing ground for prizes because they present lower R&D costs and shorter development time frames than drugs and vaccines. There is great need for innovation in TB diagnostics, because the same sputum smear microscopy has been used to diagnose it for nearly a century in resource-poor areas.

Gina: Your report focuses on prizes for global health technologies. What is a prize, in the simplest terms and how have prizes been used in other contexts?

Paul: Prizes have waxed and waned in popularity, and they have a long history dating back to the 1800s. Several European countries in the second half of the 19th century considered removing the patent system entirely and replacing it with prizes. They can be a tool for promoting innovation, and in essence are a binding commitment to reward the completion of a goal, which is similar to policy innovations like priority review vouchers (PRVs) and advance market commitments (AMCs), which also reward success.

They mean different things to different people, which makes this an interesting area. People of different backgrounds and political persuasions want to use prizes to solve a range of problems. Retrospective prizes or recognition prizes like the Nobel Prize are important and certainly motivate scientists, but they don’t motivate people to solve a particular problem or to develop a particular product. Our report looks at prizes which are aimed at achieving specific objectives and of course our interest is health products.

Gina: What are some other mechanisms that have been used to incentivize innovation in global health? How do they compare to prizes?

Amrita: Push mechanisms like grants, product development partnerships (PDPs) and tax credits have been put forward—push funding is an input, but pull funding, like prize mechanisms, focuses on the outcomes. Push mechanisms shift the risk from the product developer to the sponsor.

Paul: Push mechanisms reduce the risk of product development by providing cash up front. Even regulatory changes that reduce the costs of clinical trials could also in this category. Pull mechanisms work on the other side of the equation and increase the reward.

Gina: Can a prize substitute for a market? How?

Paul: Currently, the motivation to invest in R&D is the market share that you access in the end. The size of that market, granted by the patent system, is the reward or the degree of the incentive to conduct R&D. For some prize proponents replacing this market or creating one from scratch is a primary goal and for others it’s not a goal at all.

The current patent system enables firms to charge substantially above what it costs to make the product, but this negatively impacts patients and governments. A prize could allow you to change the R&D investment decision by aligning incentives with public health needs instead of sales revenue. By substituting prizes for markets, where they don’t exist, or by asking firms to give them up, you ameliorate the problem of access.

Amrita: When we spoke to firms, it was hard for them to accept this equation. There needs to be a way to engage firms so that they can understand these alternate ideas. For TB diagnostics, a prize is not a substitute but a complement to the market – as it can help bring new minds and solutions to address the technological challenges with developing these tools.

There are different objectives for why people want to conduct prize competitions. The X PRIZE Foundation is trying to unlock latent markets, and the AMC is trying to substitute or create a market for a product that doesn’t naturally have one. Prize4Life, which recently awarded a biomarker prize to track the progression of ALS disease, is interested in reducing the technological barriers to carrying out R&D.

Gina: Prizes seemed simple until I read your report, which highlights the importance of design. What are important design considerations and how do they affect the prize?

Paul: The prize rises and falls on the technical specifications and the amount of the prize purse. One aspect of structure that we haven’t explored as much is the number of winners. Typically, you assume that there will be one winner—a so called “winner takes all competition,” but you could structure the prize to have multiple winners.

At first I was confused as to why firms view prizes so differently from markets, but they perceive prizes to be winner take all, which markets are not. Having multiple winners, akin to controlling a certain share of the market, would reduce the perceived risk for firms. This hasn’t been implemented before.

Another important dimension of structure is whether the prize provides a final end product payment or milestones payments. Of course, you can combine the two. Both pose risks to the sponsors. If you host a milestone prize, you may never actually get the final product in hand, but a final product prize may not be appropriate in all cases.

Gina: Did you find that prizes are an effective tool? If so, under what circumstances?

Paul: Prizes are helpful when you don’t know the way forward to answer an innovation question, and you have the sense that there are a lot of solvers out there who could help find the solution. This is what economists call information asymmetry. You don’t know who’s out there and what they’re thinking; if you did you could simply contract them directly.

Amrita: The other consideration is the market potential for the product. If it’s a large market, then a milestone prize might be sufficient, but if there’s little or no market, then you need a large final product prize or a milestone prize plus some subsidy. Our report lays out a decision tree which can help funders, policymakers, practitioners and others decide whether a prize is a useful tool for a particular innovation objective.

Paul: Very broadly, you need to think about who you’re trying to incentivize that’s not currently participating in the innovation space. Once you decide that, then you can systematically think through these questions. If there are only 3 organizations in the world that can solve a problem, then it may be better to engage them directly.

The Often Awesome Army

noreply@blogger.com (Nate) — Tue, 22 Mar 2011 17:30:00 +0000

A guest blog post from our friends at the Often Awesome Army:

Our friend, Timothy LaFollette, is incredible. He is 30 years old and newly married. He is a phenomenal songwriter, a charismatic musician, a talented video editor, a fantastic cook and most of all, a really good person. He is also sick: stupid, unfair, scary and painful sick, which can't be fixed. In April 2009, at age 29, Tim was diagnosed with Amyotrophic Lateral Sclerosis - ALS (Lou Gehrig's Disease). At least five generations of Tim’s family have died from ALS, including his mother and grandmother, who both died within a year of their diagnosis.

Tim has a rare genetic strain, SOD1, which is a particularly ruthless subtype with a median survival rate of 12 months. Thankfully, Tim has survived his first diagnosis "birthday", and is approaching his second, but there have been no advances in treatment in the 28 years since his mother fell to the same illness. Tim is practically house-bound and has lost his ability to care for his basic needs.

There is a silver lining to this seemingly sad story. Because our Tim is one of the most open-hearted, pure and hilarious people we know, he's able to talk about his decline with phenomenal humor and truthfulness. Also, because our Timmy is also one of the kindest, most generous and charismatic people we know, he has an enormous community of friends fighting to make the rest of his life as wonderful as we possibly can.

We felt inexpressibly powerless and lost as we watched our amazing friend experience muscle spasms and then become increasingly clumsy. We witnessed him slowly lose his ability to move his limbs and then his respiratory function began to decline significantly, as he took shallower breaths and his voice became hoarse.

Born from an interest in caring for our friend, and supporting his wife, Kaylan, our group, the Often Awesome Army was created. Our "Army" started off as a small, close-knit group of friends. We made t-shirts, stickers and patches, and found ways to laugh through the sadness. We produced benefit rock shows and art auctions and raised money to help Kaylan buy a wheelchair accessible van, affectionately referred to as the ALSUV. We created a community of caretakers who stopped by Tim's house throughout the day, bringing him food, helping him bathe and toilet, and sometimes just to watch horror movies with him. As Tim’s illness progressed we formed the Core Care Team, of friends who volunteer their caregiving time and are trained on Tim’s equipment, to supplement the home nurse care that became constantly necessary.

Our Often Awesome Army has grown into a community of over 1,600 members. Scores of us have tattoos which signify solidarity with Tim. While each design is unique, all are based on a tattoo that Tim has on his arm: a flock of swallows that he got 10 years ago, to commemorate his mother’s passing from ALS. Like the formation of the army itself, the tattoos started off confined to a small tight-knit group of friends and eventually, people around the world have gotten tattoos in support of Tim. Many people with these tattoos had never had a tattoo before, like Tim’s ALS doctor from Duke, who proudly announced he was joining the army and going under the needle.

Tim realized early on that he had a responsibility to spread ALS awareness. This responsibility is to his family, the community of patients with ALS, their loved ones and to the larger population of people who don't even know about ALS. Though this disease affects a relatively small percentage of the population, and there is very little awareness, Tim refuses to die a silent death. ALS is not just a disease that attacked a baseball player 70 years ago; it is an ongoing struggle faced by thousands daily. Every 90 minutes, someone is diagnosed with ALS, and every 90 minutes, someone dies of ALS.

Tim's quest for spreading ALS awareness has resulted in Often Awesome: The Series, an award-winning web series about his journey with ALS. It features incredibly forthcoming interviews with Tim, his wife Kaylan, and members of the Often Awesome Army.

We invite you to watch the series, learn more about the Often Awesome Army, and support our efforts at www.oftenawesome.org.

What is electrical impedance myography?

noreply@blogger.com (Nate) — Mon, 28 Feb 2011 20:23:00 +0000

By now, we imagine you have heard the news (especially if you read our last blog entry or the New York Times) that the $1M ALS Biomarker Prize has been won. It was awarded to Dr. Seward Rutkove for his development of electrical impedance myography (EIM.)

But what exactly is electrical impedance myography?

Here's a blurb from The ALS Forum that provides some insight:

"Currently, researchers rely on death or use of a ventilator as the primary endpoints in ALS trials, measures too crude and slow to quantify drug effects early. The new test tracks disease progression with a noninvasive device that measures how electrical current travels through muscle, which degenerates as ALS progresses. Scientists can also measure muscle conductivity between needle electrodes implanted into muscle, but those methods are harder to perform and less reliable than the new device, besides being painful for patients. Rutkove's handheld device measures the electrical field generated when current runs through the muscles underneath electrodes placed on the skin.

The $16,000-$20,000 unit attaches to a laptop or personal digital assistant-like device. The test takes about 20 minutes and detects abnormalities even before a person notices muscle weakness. Rutkove has also suggested that electrical impedance myography might help doctors diagnose ALS, although it may not be able to distinguish ALS from other neurological conditions that affect muscle (Rutkove, 2009). The method does differentiate between neurogenic ALS and some myopathic conditions such as inflammatory myopathy (Garmirian et al., 2009)."

(If you haven't already, check out The ALS Forum, a great collection of the latest news and most up-to-date resources in the ALS field at www.researchALS.org.)

And here is a description of the technology in Dr. Rutkove's own words. After a 2009 review of potential ALS biomarkers published in The Lancet did not include a mention of electrical impedance myography, Dr. Rutkove wrote a letter to the editor that details his work and the potential impact of EIM.

Now, firmly in the limelight, Dr. Rutkove's technology is attracting interest from drug developers eager to make ALS clinical trials cheaper, faster, and more efficient. Dr. Rutkove has co-founded Convergence Medical Devices to create and market a version of the technology that can easily be used in clinical settings.

And while this biomarker has no direct therapeutic value, it holds the promise of accelerating the discovery of treatments or a cure for this disease--the mission of Prize4Life and the hope of thousands of patients and families around the world.

$1M ALS Biomarker Prize Has Been Won!

noreply@blogger.com (Nate) — Wed, 16 Feb 2011 18:23:00 +0000

In 2006, the founding members of Prize4Life organized a conference with some of the leading minds of the ALS research community and the biotechnology industry to answer a simple question: why, after more than 140 years since it was first described in scientific literature, is there still no effective treatment for ALS?

Participants at the conference identified several key challenges in the field, but perhaps the most fundamental obstacle that had yet to be overcome was the need for a biomarker, a tool that could reliably track the progression of the disease in patients during clinical trials. Because the progression of ALS is highly variable among individuals, the only ways that researchers could gauge whether a potential treatment was having any effect was to measure survival time or use a subjective survey of a patient's ability to walk, talk, speak, and swallow. The ambiguity of these measurements meant that clinical trials needed to enroll a large number of patients and last for a long period of time. Expensive and often inconclusive clinical trials meant that industry had little incentive to invest in drug development and any progress in research would be painstakingly slow.

Prize4Life now had a clear objective. In 2006, we partnered with the open innovation platform InnoCentive to launch the $1M ALS Biomarker Prize with the goal of identifying a biomarker that could more sensitively track the progression of ALS and dramatically reduce the cost of clinical trials. It was our intention to catalyze a breakthrough, a leap forward in ALS research that would accelerate the development of a treatment for the thousands upon thousands of people battling this disease across the globe.

Now, five years later, we are proud to announce that a breakthrough has been achieved. Our Scientific Advisory Board, made up of the top minds in the ALS research and biotechnology communities, unanimously voted to award the million-dollar prize to Dr. Seward Rutkove, a neurologist at Beth Israel Deaconess Medical Center in Boston. The New York Times profiled Dr. Rutkove and the Prize4Life award.

Dr. Seward Rutkove’s biomarker, using a method called electrical impedance myography (EIM), sensitively measures the flow of a small electrical current through muscle tissue. The current travels differently through healthy and diseased tissue, and by comparing the size and speed of the electrical current, EIM can accurately and efficiently measure the progression of the disease. Read more about the EIM technology here.

EIM technology in use. Photo credit: Convergence Medical Devices

This biomarker will make ALS clinical trials cheaper, faster, and more efficient; effectively cutting the overall cost of these trials in half, creating an incentive for industry to invest in ALS, and accelerating the progress of potential therapies through the drug development pipeline.

The development of Dr. Rutkove's biomarker is not only a game-changer for ALS research, it is a validation of the prize model's role in driving biomedical innovation. The $1M ALS Biomarker Prize is the largest prize ever awarded in response to a specific medical challenge. The million-dollar purse leveraged more than $4M in investment from teams competing for the prize. And more than 1000 solvers from over 20 countries signed up for the challenge, bringing new minds and new ideas into the fight against ALS. You can learn more about the impact of the prize on biomarker research here.

Now, we at Prize4Life are turning our attention to overcoming the next obstacle: the identification of promising drugs that can slow the progression of ALS. It is the focus of our second million-dollar challenge, the $1M ALS Treatment Prize.

We invite you to learn more about Prize4Life and join our efforts as we continue the march toward a cure.

Patrick the Optimist: Exciting Times

noreply@blogger.com (Nate) — Wed, 15 Dec 2010 19:08:00 +0000

If you don't know why Patrick is an incurable optimist, read more about his story here.

Patrick, an artist and MND sufferer, is on a quest to create 100 portraits of fellow patients before he loses the ability to paint forever. Here is a brief glimpse into his life, an entry posted on his blog that describes his participation in a study to identify a blood-based biomarker of his disease.

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Research into MND is important. Very important. Clearly this is a horrible disease that wrecks lives. It kills people before their time, slowly, cruelly, relentlessly. So on an abstract level, the importance of research is obvious. If we could understand how MND works, then we could devise a treatment or even a cure. This would save thousands of lives every year. But this importance is abstract, you can understand it on an intellectual level, but can you feel it coursing through your veins, in your soul? There is one group of people for whom the importance of research is visceral, a basic, urgent, desperate need – like the need to breathe.

These are the MND sufferers and their families, the people that live with MND on a daily basis. But why is it so important to them? Even if a discovery was made today, that was to lead to a cure, these things take years, and MND moves very fast – any discovery made today will probably be too late for them, and too late for me. So why do many sufferers spend so much of the last few months and years they have left, raising money to power this research? It is like the landowner who plants a tree, knowing he will not live long enough to walk beneath it’s boughs. We need to know that MND will be stopped, that our children’s generation will not lose five thousand people a year to the dread disease that took their father, brother, or friend.

But these are exciting times. We have some good people on our side. Some of them, like Dr Emily Goodall have lost loved ones to MND, and this drives their research, fired by love, loss and the determination that comes with grief. But most of them do not have a personal connection to MND, yet they are united by a desire, a zeal that goes beyond doing their job well. If you look into their eyes, as I have done, you will see passion in them – passion for the prize of stopping MND and passion for the chase. This is not a stagnant field, MND research is going at a breakneck pace. In the UK we have some of the best MND scientists in the world, people like Dr Martin Turner and Dr Ammar Al-Chalabi, both of whom have recently made important discoveries, which have excited me and inspired me to write this blog. Ammar, working with an international team, discovered a gene in chromosome 9 that is involved in sporadic MND. This is big news, a milestone, and may well turn out to be a big leap forward on the road to that glittering prize. And Martin’s discovery? Well, I shall tell you about that in a minute, because I was involved with that one.

It is entirely normal for patients with MND to speculate about their disease, about what caused it and why – and I am no different. In my opinion this is part of the process of taking control of the disease – not letting it control you, and is perfectly healthy. Historically the only contact a patient would have had with a neurological specialist would have been fifteen minutes with his doctor every three months. Many patients felt alienated and resentful towards the scientists involved in MND research. There was not much understanding of what they are doing or feeling of any common ground. The MND association realised this and started making moves to get patients involved in research, to help bridge the patient/scientist gap. By the time I was diagnosed, this process was in full swing, and I answered a little advert in my local branch newsletter asking for volunteers for a project in Oxford looking for a MND biomarker. The person running the project was called Dr Martin Turner.

There is currently no test for MND. Any diagnosis is made clinically, meaning that a neurologist will observe your symptoms as they progress and then test for and exclude any other disease that could produce a similar effect. A biomarker is a test for MND, it could be a blood test or a brain scan, or a number of other things. A test would speed up the diagnosis process and make it more certain, but it would also have another, very important use. Because there is no test for MND, there is no easy way of testing new MND drugs quickly and cheaply. The only way at present is to give the drug to 100 patients, give a placebo to another 100, wait 18 months and then count how many are dead in each group. This process is slow, and as you can imagine, very expensive, and limits how many new treatments can be tested. If we had a biomarker then new drugs could be tested on small groups of people in a fraction of the time, and at a fraction of the cost. This would speed up the pace of research enormously. An MND biomarker is a prize of incredible value – priceless really.

I have been going to Oxford every six months now for two years. I spend a day there each time, having cognitive tests, MRI scans, blood tests and a lumber puncture. And I get to talk to Martin Turner. Martin is kind, and generous with his time, a lovely man. I am very lucky, through talking to Martin, to have been given a window into the world of MND research, and I like what I see there. I have been inspired by Martin to read more and more about the state of MND research and the people involved in it. I now want other people to share the confidence and excitement I have in what they do.

You can imagine my excitement then, when Martin told me he had actually found a biomarker for MND, by looking inside (amongst others) my brain! It was like entering a prize draw to win a car, and then actually winning it. But then what happened next was, I had to sit on the knowledge for months while Martin feverishly prepared his paper for publication. So I was very pleased when it was finally published last week and I could tell you about it. This is amazing news, brilliant news – all the more so for me because I bore a part in its making.

The MND Association should not be forgotten here either. They got me to Oxford and they helped fund Martin’s research. But while we certainly have a lot of good people on our side, it is not an army by any means. MND research is underfunded and we need more money, a lot more money – I can not be bitter however, these are exciting times, exciting times indeed.

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You can follow Patrick's blog at patricktheoptimist.org.

Another blogger we follow, Anne Marie Schlekeway of KissMyALS.com, passed away last week. Anne's unflinching honesty about the disease and her persistent sense of humor served as an inspiration for ALS patients the world over. Our thoughts are with her family... she will truly be missed. You can read an article about Anne's story here.

A Brief Interview with The CEO of Brainstorm Cell Therapeutics Re: Upcoming ALS Clinical Trial

noreply@blogger.com (Nate) — Tue, 23 Nov 2010 14:37:00 +0000

On October 11th, Brainstorm Cell Therapeutics announced that the Israeli Ministry of Health had granted clearance for a Phase I/II clinical trial using the company’s autologous NurOwn™ stem cell therapy in patients with ALS (pending completion of validation studies).

To find out more about what this means to the field, and why Brainstorm has decided to focus on ALS research, I spoke with the Director and CEO of the company, Mr. Rami Efrati. Mr. Efrati has worked with Brainstorm for three years, having previously served for seven years as Vice President of Sales, Business Development, and Marketing at NICE Systems.

In a nutshell, Brainstorm’s therapy involves extracting stem cells from a patient’s bone marrow, inducing these cells to differentiate into supportive neurological cells, and injecting these cells back into the same patient at the site of damage. Because the stem cells are taken from a patient’s own marrow, there is a reduced risk of the body rejecting them once they are re-transplanted. The adult nature of the stem cells also allows Brainstorm to sidestep any ethical or moral controversy associated with embryonic stem cell research. While the therapy has potentially far-reaching applications to a variety of neurological diseases, Brainstorm’s focus remains, for the time being, on ALS.

“Brainstorm originally started working on Parkinson’s disease. Two years ago, our company made the decision to focus our efforts on diseases which would bring us as quickly as possible to clinical trials in order to help people,” said Mr. Efrati. As ALS was among the diseases that were candidates for this targeted approach, “…we wanted to invite ALS patients to come to discuss their experience with the disease. I kept hearing the name Avichai Kremer [CEO and co-founder of Prize4Life,] and I said, ‘who is he?’ We invited him in, and we became good friends. I came to believe in the mission of Prize4Life, and believe in Avi’s fight against ALS.”

Avi’s enthusiasm that ALS research was at a tipping point was apparently quite infectious. Choosing to focus on a disease that was ripe for a breakthrough was not just a marketing decision; it was an attempt to get a promising therapy to suffering patients quickly. As Chaim Lebovits, President of Brainstorm, said shortly after the announcing of the trial, “…the greatest satisfaction comes from saving a human life, not to mention thousands of lives; G-d willing, I am hopeful we can achieve that.”

But the decision was not received well by those wary of the return on investment. ALS is considered an orphan disease, meaning that because it is so rare (a disease with orphan designation must affect fewer than 200,000 individuals according to US criteria,) there is little financial incentive for companies to invest in the research. “People asked me, ‘Are you crazy? This is not logical,’” Mr. Efrati recalled. But the figures seemed more encouraging to Brainstorm. “I explained to our skeptical investors ‘There are at least 100,000 people with ALS in the Western World [author’s note: and 600,000 worldwide]. This means an estimated $6 billion market. And our therapy has the potential to be applicable to many disorders of the central nervous system, such as Multiple Sclerosis and Parkinson’s disease’. I think they found this persuasive and worth the many risks.” All told, Brainstorm estimates the potential global market for these diseases at $214 billion.

The trial will begin after the screening of patients. “The clinical trial will be headed by medical doctors at Hadassah Medical Center, under the direction of Prof. Dimitrios Karussis,” explained Mr. Efrati. “Because this is the first time we are treating a human being, the first phase of our trial will be focused entirely on safety.”

But researchers are hopeful that after the safety of the procedure is assured, they will be able to track the efficacy of the treatment. “Imagine that soon, if a doctor tells you that you have ALS, he or she can also say that there is a treatment that will slow or stop the progression of this disease. This will be an exciting moment.”

Certainly there are thousands of eyes on this trial, eager to share in that excitement. The trial will recruit 24 patients and take place in Jerusalem. Potential candidates will be screened by a panel of doctors affiliated with the Hadassah Medical Center.

For more information on the trial, visit the National Institute of Health’s database of clinical trials here.

To learn more about Brainstorm Cell Therapeutics, you can visit their website at www.brainstorm-cell.com.

For more information about the Hadassah University Medical Center, go to www.hadassah.org.il/english.

The Two Fronts

noreply@blogger.com (Nate) — Thu, 11 Nov 2010 16:00:00 +0000

As we take time to honor the veterans who have served our country, it is important to remember that for many, the battle continues to rage long after they return home.

Men with any history of military service are at nearly a 60% greater risk of being diagnosed with ALS than men who did not serve in the military. The study by researchers at Harvard University's School of Public Health showed that military personnel have an increased risk regardless of when or where they served, and regardless of whether they experienced combat.

The United States and Canada offer benefits to veterans suffering from ALS. The US Department of Defense funds ALS research. A study by researchers at the Veterans Affairs Medical Center in Bedford, MA pointed to the link between head trauma and ALS as one possible explanation as to why ALS has been diagnosed in military veterans at higher rates. Others have posited increased exertion or exposure to chemicals as potential causes.

The connection between ALS and military service is undeniable, but the reasons behind that connection remain, for the moment, unclear. As with so many of the other mysteries associated with ALS, we are left to wonder simply, why?

Now, there is a tool that might help us answer that question. Recently, the Centers for Disease Control launched the National ALS Registry, an online platform that collects, manages, and analyzes data about people with ALS. It is hoped that the registry will help answer some of the most fundamental questions about the disease, not only telling us why certain groups are more prone to develop ALS, but also providing researchers and scientists with critical information that will improve diagnosis and care, and speed up the development of treatments.

If you or a loved one have ALS, please join the registry today. Together, we can honor the bravery of veterans and ALS patients the world over by taking another step towards a cure.

If you want to learn more about the connection between ALS and the military, read this excellent paper written by the ALS Association.

Another Amazing 5K4Life!

noreply@blogger.com (Nate) — Fri, 29 Oct 2010 17:17:00 +0000

If you weren't in Kendall Square last Sunday, you missed out on a great race! If you were, thanks for participating and/or sorry for making you sit in your car while the horde of runners zoomed by!

The second annual 5K4Life was a great success. We had 429 runners register, and we raised over $30,000 to support ALS research!

You can see a full listing of the results from the race here.

And feel free to peruse some photos from the 5K in our gallery!

All of us at Prize4Life want to thank the hundreds of people who made this event possible. In addition to all of those who ran and raised money, we had 37 extremely dedicated volunteers who helped us with everything from bag stuffing and water distribution to manning the registration tables and serving up pasta and sandwiches.

We also want to give a big shout-out to two teams in particular that really made the 5K4Life shine, Team Hammy and Team Ashley.

You've gotta love the level of enthusiasm Team Hammy brought! They were our top team fundraiser, contributing $5,510 to support our mission of accelerating the discovery of treatments and a cure to ALS.

Team Ashley sent us scrambling for more registration cards, mobilizing 83 runners to participate in the race! The eponymous Ashley Agri had registered for the 5K4Life weeks in advance, but she was involved in a car accident that left her in critical condition and unable to compete. To show their support, Ashley's friends and family took up her mantle and ran for her. While Team Ashley was in high spirits for the race, the incident is a stark reminder of how fragile life can be and how so many of us take the ability to run or even walk for granted.

To all of those who ran or helped others run in support of the thousands of people currently afflicted with ALS who could not, we give our deepest and most heart felt thanks. And our best wishes and hopes for a speedy recovery to Ashley!

And if you are feeling bummed that you missed out, there's always next year!

ALS-TDI Hosts 2010 Leadership Summit

noreply@blogger.com (Nate) — Mon, 18 Oct 2010 18:20:00 +0000

On October 3rd and 4th, the ALS Therapy Development Institute, our colleagues in Kendall Square, opened their doors for their sixth annual conference and open house, and Prize4Life was in attendance.

One of the great things about ALS-TDI’s Summit is the lengths they go to ensure the event is open and comprehensible to patient and families, not just researchers and scientists. As open and comprehensible as an incredibly complex and evolving scientific field can be, of course…

The research symposium portion of the Summit featured speakers such as Dr. Steve Perrin, CEO and Chief Scientific Officer of ALS-TDI, Dr. Fernando Vieira, Director of In Vivo Validation at ALS-TDI, Dr. Merit Cudkowicz, ALS Clinic Director at Mass General Hospital and Co-Founder of the Northeastern ALS Consortium, and several others. Topics ranged from drugs currently in the development pipeline and new mouse models, to the ongoing controversy over stem cells and which clinical trials show the most promise for participants.

This article in the MDA/ALS Newsmagazine covers many of the presentations and discussions in great detail. And ALS-TDI has also posted video of the conference on its website, though you do have to register with an email address to view it.

Two portions of the day were of particular interest to us at Prize4Life: Dr. Cudkowicz’s and Dr. O’Neill’s (of Biogen Idec) discussions on the need for a biomarker to advance research.

Dr. Cudkowicz acknowledged some of the frustration she has witnessed in the ALS community at the fact that the disease was discovered in the late 1800’s and yet there remains no effective treatment. But she pointed to the relatively rapid progress following the discovery of a gene associated with ALS in 1993, which brought new scientists, new minds, and new ideas into the ALS field. More recently, she discussed how the 2006 correlation of TDP-43 with sporadic ALS caused scientists studying TDP-43 in other fields, such as dementia, to begin to think about ALS and how a therapy might potentially be developed.

In order to spark a leap forward in research progress, Dr. Cudkowicz says a biomarker is needed. The vast majority of ALS treatments fail in Phase II trials. This makes the development of drugs both incredibly time-consuming and incredibly costly. A biomarker dramatically shortens the time required for drug development, thus driving down the overall cost of that development. If such a biomarker were discovered, “an explosion of [ALS] therapies would result,” according to Cudkowicz. When asked by patients what they can contribute, it is towards the discovery of a biomarker that Cudkowicz points them—encouraging them to donate blood and tissue samples which are critical tools for researchers on the biomarker quest.

Dr. Gilmore O’Neill, Vice President of Experimental Neurology at Biogen Idec, also emphasized the importance of a biomarker. He explained that any trial has three possible outcomes. A positive result is, of course, the most desirable—when a drug slows or arrests the progress of a disease. But the least desirable result is not a negative study, but rather a failed one—a study where not only does the drug not have the desired effect, but researchers cannot even be certain if the drug hit its intended target.

In essence, failed trials tell us nothing, and they do not advance research in the way that negative results can. An effective biomarker means, in Dr. O’Neill’s words, that researchers “…can throw out the garbage very quickly.” Without a biomarker, trials are forced to include more patients, must last longer, and are more likely to yield uninterpretable (failed) results.

Dr. O’Neill discussed biomarkers in the context of drug development for several other diseases—his underlying theme being the need for an ALS biomarker. At Prize4Life, we wholeheartedly agree. We believe the discovery of a biomarker for ALS is so important that we’ve put up a $1 million prize to spur on research.

And there has never been an organization more anxious for a reason to give away its money.

Join us on October 24th for the 5K4Life

noreply@blogger.com (Nate) — Tue, 12 Oct 2010 18:41:00 +0000

In 16 years with the New York Yankees, Lou Gehrig played in 2,164 games. From 1925 to 1939, he played in 2,130 consecutive games. He played sick, and he played hurt. He played through slumps and stardom. Whenever Gehrig’s number was called, he stepped up to the plate. You aren’t born with a nickname like ‘The Iron Horse;’ you have to earn it. For 14 years, there was no force on heaven or earth that could keep Henry Louis Gehrig from playing baseball.

And then, on May 2nd, 1939, after months of steadily declining performance, Lou benched himself and ended his streak. In June of that year, he received the diagnosis: amyotrophic lateral sclerosis. ALS. Lou Gehrig’s disease. He would never play again.

More than 70 years later, there is still no cure for ALS. And that’s why Prize4Life was founded. Our CEO was diagnosed with the disease in 2004 at the age of 27. He knew that existing resources and research were not enough—something was needed to bring new minds and new money into the fight. Our model fills that need. Prize4Life offers large, cash prizes for targeted scientific breakthroughs that will help accelerate the search for a cure.

On Sunday, October 24th, we will host our second annual 5K4Life, a road race aimed at raising awareness and funds to help us achieve our mission and bring us closer to eradicating ALS once and for all.

The race will take place at 11AM in Cambridge Center. There will be food, refreshments, music, gifts, and prizes for the top finishers and fundraisers. For more information, or to register for the race, visit www.5k4life.org.

Today, 30,000 Americans have ALS. Most will die within 3 years. The disease will strip from them all voluntary muscle movement. They will not be able to feed themselves, let alone run.

But you can. Stand in solidarity with the patients and families struggling with this disease, and join us on October 24th.

Upon his death, Gehrig’s wife Eleanor said, “It was strange because there was no particular reason to keep playing without a break, no particular compulsion–except the fascination to add one more day, one more week, whatever you lost.”

As long as there is no cure for ALS, the reason seems clear: one more day, one more week may be all some people have. But we can change that.

For more information on Prize4Life, visit us at www.prize4life.org.

The Candle Problem

noreply@blogger.com (Nate) — Mon, 20 Sep 2010 19:45:00 +0000

I have a riddle for you!

On a table, there’s a candle, a book of matches, and a box of tacks. But here’s the problem: no one knows how to fix the candle to the wall without the wax dripping onto the table below.

Representatives of the candle, match, and tack industries have poured millions of dollars into studies in order to crack the case. A $20 million effort attempted to jam tacks through the candle to attach it to the wall. A $30 million study looked into the possibility of melting the wax on one side of the candle to make it stick to the wall. Neither idea worked.

Desperate to find a solution, the Big 3 decided on a novel approach—they issued a public challenge and promised a large sum of cash to whoever could end their candle dilemma once and for all.

An out-of-the-box thinker came to the rescue. “Why not, you know, take the tacks out of the box, and use that?”

SUCCESS!

But is that how it works in real life? Dan Pink, a career analyst and former speechwriter for Vice President Al Gore, contends problem-solving is slightly more complicated than that.

In his TED speech entitled ‘The Surprising Science of Motivation,’ Pink references a study that shows how individuals that are promised a reward for solving the candle problem actually perform WORSE than their un-rewarded competitors. On the surface, the finding doesn’t really make sense—isn’t money the ultimate motivator in our market-driven society?

(By the way, if you’re not familiar with TED, it’s an incredible series of talks that allow some of the brightest minds in the world to widely share their ideas. Check it out at www.ted.com.)

There are two reasons why the candle bonuses failed. First, rewards are excellent at narrowing our focus to solve a very specific problem, but they’re not nearly as useful in helping spur broad, creative thinking. Second, a reward must be tied to some intrinsic motivation to be truly effective—unfortunately, most of the study participants didn’t feel any personal desire to keep the table wax-free, they just wanted the cash.

At Prize4Life, we’re not just throwing money at a problem. Our prizes are highly focused on specific outcomes. Find a biomarker to track the progression of the disease and/or add a promising candidate (with a powerful effect on an ALS mouse model) to the drug development pipeline, and you’ll be rewarded. We’ve taken a broad goal—curing ALS—and narrowed the focus to these key challenges that prizes can help meet. By solving these smaller problems, we are opening the floodgates, and industry will pour resources into the search for a cure.

In addition, the people competing for our prizes have a powerful intrinsic motivation. Whether they know someone with ALS or not, helping to find a cure for this horrific disease means becoming part of something important—giving a normal life to thousands upon thousands of people.

The moral of this story: money can’t solve everything. But if used right, it sure can make a difference.

For another inspiring and fascinating discussion on how and why problems should be shared with a more extensive audience of potential ‘solvers,’ watch Ted Andersen, curator of the TED conferences, in his talk entitled ‘Crowd Accelerated Innovation.’

Challenge.gov and The French Connection

noreply@blogger.com (Nate) — Mon, 13 Sep 2010 20:18:00 +0000

In the early 19th century, Napoleon, Emperor of the French, faced quite the dilemma. His armies were stretched across the European continent, and there was no easy way to deliver much-needed brie and escargots to the front lines.

Napoleon knew that an army marches on its stomach, and so he offered a cash prize of 12,000 francs to any inventor who could devise a cheap and effective method of preserving large quantities of food. Nicolas Appert, a French candy-maker, began experimenting with a method of preserving food by placing it in glass jars, sealing them with cork, and boiling the jars in water. In 1810, Appert presented his invention to Napoleon and was awarded the 12,000 francs.

As a general rule, the Obama administration tends to avoid any potential association with someone like Napoleon, but even an ardent Francophobe has to admit his idea of using prizes to solve big problems was a good one. And in that spirit, the White House Office of Science and Technology Policy recently announced the launch of Challenge.gov, an online platform that solicits the ideas of ‘citizen solvers’ and applies them to a host of national problems. Challenge.gov features over 35 challenges posed by more than 15 government agencies. Some of the challenges include:

• The Kids.Gov ‘How Do I Become President?’ Challenge: This being one of the most frequently asked questions of Kids.gov, a $5,000 prize will be awarded to the creator of the best visual aid that explains the process.

• The NASA Green Flight Challenge: In order to spark the development of an aircraft that can fly 200 miles in less than two hours using the energy equivalent of less than one gallon gasoline per occupant, NASA is offering a $1.5 million prize.

• The Progressive Automotive X Prize: Pairing with the eponymous insurance agency, the Department of Energy is offering $10 million to any one who can build a safe, affordable, production-ready vehicle that gets 100 miles to the gallon or greater.

• The Apps4Africa Contest: Our personal favorite at Prize4Life because of its incredibly catchy title format, this challenge offers $15,000 to the designers of open digital tools that can be used to address community challenges such as healthcare, education, and governance in East Africa.

According to Tom Kalil, Deputy Director for Policy in the White House Office of Science and Technology Policy, “These challenges are just a handful of those featured on Challenge.gov and just a taste of what’s to come. By making it simple and free to post challenges, Challenge.gov will accelerate agency adoption of prizes as a means of spurring innovation.”

Prize4Life is eager to see this platform succeed. Just like our prizes for ALS breakthroughs can act as a tipping point in the search for a cure, so too can Challenge.gov and similar efforts act as a tipping point for inducement prizes as a whole. The prize model has an enormous potential to leverage new investment in any number of fields and create solutions to problems that have plagued us for too long.

Nicolas Appert was not a scientist. He couldn't explain why his canning method worked; it would be 50 years before Louis Pasteur discovered why food spoiled. He was not a wealthy man. In fact, the factory that Appert bought with his prize money was destroyed by Allied soldiers when they invaded Paris, and Appert died penniless.

In so many ways, Nicolas Appert was an average man, no more than a footnote in history. But his invention has helped feed the world, saving an untold number of lives. Appert had no grand fortune, no great education, but he did have an idea that would change the course of history.

And all it took was a prize to bring it to light...

Cutting-edge ALS Technology

noreply@blogger.com (Nate) — Tue, 07 Sep 2010 13:48:00 +0000

Until medicine proves otherwise, technology IS the cure…

That’s the mantra of the ALS Residence Initiative, a group spearheading the construction of a series of permanent residences specifically designed for individuals living with the fatal neurodegenerative disease, amyotrophic lateral sclerosis. The first such residence officially opened in Chelsea on August 13th, and it comes equipped with a technological payload that would make a nuclear submarine commander proud.

Each resident has a computer control panel mounted on his or her wheelchair. Controlling the computer mouse using whatever muscular movement they still possess (their head, eyes, or fingers,) the resident can issue commands that are beamed via infrared transmitters to a series of receivers scattered throughout the center. The commands are then bounced to a master computer that opens doors, turns lights on and off, draws the blinds, takes room service orders, and even operates toilets. The end result is a smart house that provides once unimaginable levels of independence to individuals suffering from neurodegenerative disease.

The center came to life through the work of Barry Berman, CEO of the Chelsea Jewish Foundation, and Steve Saling, a 41-year old former landscape architect who was diagnosed with ALS four years ago. The Chelsea Jewish Foundation operates the Leonard Florence Center for Living, a 100-bed nursing home in Chelsea. In addition to the ALS residence named after Saling, the Leonard Florence Center has also built a residence designed for multiple sclerosis patients.

Asked what he would do if he lost the ability to move his computer mouse using his eyes and head, Saling pointed to technology currently in development that would allow ALS patients to control computers with their brain waves. That technology would be the subject of the keynote speech at the 4th Annual ALS Roundtable that followed the grand opening of the residence.

Prize4Life partnered with the Massachusetts Chapter of the ALS Association to launch the Roundtables. Recognizing that there are many organizations across Massachusetts working to cure ALS, Prize4Life co-led the charge to bring these groups together so that they could share information and best practices and identify opportunities to work together towards a common cause. We are enormously proud of what the Roundtables have yielded, including the opportunity to learn from Dr. Leigh Hochberg the latest developments in the brain wave technology known as ‘BrainGate.’

BrainGate aspires to literally turn thoughts into action. A chip is placed in the brain and records signals that correspond to imagined limb movement. Decoder software and hardware then translate these signals into usable commands for an external device. In Saling’s case, the external device would be a computer mouse that would allow him to ‘think’ the cursor across the screen. But BrainGate’s imagination reaches much farther than that. Scientists hope that the technology can one day be used to control prosthetic limbs, or even coupled with electronic stimulation so that the mind can bypass damaged nerves and move once-paralyzed muscles.

But for the time being, ALS patients like Steve Saling must be content with the simpler joy of turning a light off when they are ready to sleep and merely dream of much more complex joys like walking and talking. Steve’s son, Finn, was born just one month before Steve was diagnosed. When interviewed for an article in the Boston Globe, Steve described his role as a father. “I’m right now watching my brother canoe to shore with Finn in his lap. I wish that could be me.”

While the Leonard Florence Center for Living Steve Saling Residence in Chelsea is a quantum leap forward in technology, it is, sadly, not a cure. It provides independence to be sure, but not the freedom to hold one’s child in one’s arms. To achieve that, we have no alternative but to bring together the minds, money, and breakthroughs needed to eradicate ALS.

That’s where Prize4Life comes in. Prizes have the ability to attract new ideas from new sources. And when those prizes are highly focused on results, are ours are, they can drive breakthroughs that will accelerate progress toward a cure. Awarding prizes in the biomedical field is a new, relatively unproven model. But the old ways simply haven’t gotten the job done.

Learn more about our prizes here.

For more information on the Leonard Florence Center for Living, you can visit www.leonardflorencecenter.org.

For more information on BrainGate, visit www.braingate2.org.

Drug Development for Neurodegenerative Diseases Part 4

noreply@blogger.com (Melanie Leitner) — Mon, 02 Aug 2010 14:57:00 +0000

This next installment of blog coverage from the Drug Development for Neurodegenerative Diseases conference organized by marcus evans focuses on the much buzzed about topic of regeneration.

Neurodegenerative diseases such as Alzheimers Disease, Parkinson’s Disease, Huntington’s Disease and Amyotrophic Lateral Sclerosis (ALS) are characterized by a significant and increasing loss of neurons. In the case of ALS, loss of the neurons that control voluntary muscle movement (motor neurons) underlies the progressively debilitating symptoms experienced by ALS patients. Even before patients start to notice problems with their motor function, changes have already begun to occur. It is estimated that 30-50% of a patient’s motor neurons have already degenerated by the time an ALS diagnosis is made.

As neurons begin to die, the remaining motor neurons can partially compensate for this loss (by increasing the strength and number of connections to the target muscle), but eventually the tipping point comes when too few neurons remain to properly control the muscle and clinical symptoms begin to manifest.

What can we do about this? Ah, regenerative medicine!

Speaker Judith Kelleher-Anderson, President and Chief Scientific Officer at Neuronascent, Inc., described to the audience that much of the focus in regenerative medicine has been placed on invasive therapies involving transplantation of healthy cells into the diseased area. These studies have led to a handful of clinical trials in which preparations of either human embryonic stem cells or human neural stem cells have been surgically transplanted in patients with Parkinson’s Disease, spinal cord injury (SCI) and more recently ALS.

After transplantation, these healthy cells face the formidable challenges of both maturing into the appropriate type of cell - a dopaminergic neuron for PD, an oligodendrocyte for SCI, or a motor neuron for ALS - and then rewiring themselves back into the existing cellular network. Functional recovery for patients depends on both of these steps happening.

The invasive nature of these regenerative therapies and additional safety and efficacy concerns (ie: potential to form tumors, uncertainty whether stem cells will integrate and restore function, and tissue graft rejection) have caused some researchers to pause and consider if there is another, less traumatic way to replace damaged cells in the CNS.

Kelleher-Anderson and her colleagues at Neuronascent are among the researchers considering an alternative approach in regenerative medicine. This line of research takes advantage of the revolutionary discovery made in the 1990s that, just as adults have the ability to generate new muscle, skin, and blood cells, adult brains have the ability to generate new neurons (you have to scroll down a half a page to get to the reference). This remarkable property opens up another avenue for therapeutic intervention for treating neurodegenerative disease. Rather than surgically adding back neurons, perhaps it is possible to deliver drugs that can stimulate the brain’s natural ability to generate more neurons.

Kelleher- Anderson presented some early results from her team at Neuronascent. They have identified a candidate small molecule drug that seems to enhance the ability of human neural stem cells to generate new neurons in culture. When they tested this candidate drug in a mouse model of aging, they saw that the drug could also enhance generation of neurons in the brains of treated mice and - even better - they saw that drug treatment could reverse the learning and memory deficits normally associated with aging.

Encouraged by these findings, they tested their drug in a rat model of neurodegeneration and found similar beneficial effects – new neurons were born and rats showed improvements in motor function. One exciting interpretation of these observations is that the newly generated neurons integrated into the existing neuronal circuitry to restore motor function in animals – but this awaits further studies.

The field of regenerative medicine is growing and fostering innovative ways to address the needs of patients with neurodegenerative diseases. From transplanting stem cells to harnessing the body’s own regenerative capacity, researchers are energetically working towards this goal. The road to safe and effective regenerative therapies has thus far been studded with both success and failure. Nevertheless, the road of regenerative medicine is one that many researchers and patients alike believe is worth traveling.

---Sheila Menzies

Drug Development for Neurodegenerative Diseases Conference Part 3

noreply@blogger.com (Melanie Leitner) — Mon, 26 Jul 2010 17:10:00 +0000

After a bit of a hiatus (following the departure of Meghan Kallman, our fearless former Communications Manager), we now bring you Part III of our blog series covering the marcus evans 2nd Annual Drug Discovery For Neurodegeneration Conference (see Part I here and Part II here).

Switching tracks, the next speaker, Dr. Gregory Stewart, Director of CNS Drug Therapy R&D for Medtronic, offered a slightly different perspective on therapeutic development in his talk entitled: Targeted Drug Delivery for Neurodegenerative Disease: A New Hope.

Medtronic is the world’s largest medical technology company. One of their major markets is drug-infusion pumps. With current revenues over $1.4B annually, drug delivery is a good market to be in!

Dr. Stewart discussed many of the reasons why drug developers should be thinking carefully about drug delivery. Questions of safety, cost, speed, compliance, and intellectual property may all be factors influencing drug delivery. As one example, if a patient takes morphine orally for pain relief, they need 300 times (30,000%!!!) more drug then if the morphine were delivered locally (via a pump for example).

As another example, patients taking a drug orally can get effects (including side effects) anywhere in their bodies, as most organs of the body will be exposed to a given drug (whereas, as Stewart pointed out, using a pump limits exposure of a given drug to the organ of interest). This can be a good thing, as when you take an aspirin for a headache and then go on to stub your toe (the aspirin can affect the pain in both places) but can be less good when you take that same aspirin for your headache and it upsets your stomach.

Targeted delivery has the further benefit of bypassing the liver (which constantly breaks down and filters out substances in your body), which can lead to a reduction of drug dosage at the desired target. Dr. Stewart provided several other compelling benefits for use of targeted delivery for drugs, particularly when the brain is the target.

In Medtronic’s view, the key failure of biotechnology to date has been the problem of failing to understand the nuances of drug delivery. Now that we have a vastly improved understanding of delivery principles, the drug development community is poised to make great advances, particularly at the final frontier of crossing the blood-brain-barrier and getting drugs directly to the brain and spinal cord.

With the increasing number of big and bulky drugs like antibodies and cell-based therapeutics being developed for ALS, drug delivery issues will only continue to grow in importance. Dr. Stewart urged drug developers to think about drug delivery issues early in the process, as this will impact the ultimate efficacy of any candidate therapeutic.

Drug Discovery for Neurodegenerative Diseases Part II

noreply@blogger.com (Melanie Leitner) — Fri, 23 Jul 2010 20:00:00 +0000

After a bit of a hiatus (following the departure of Meghan Kallman, our fearless former Communications Manager), we now bring you Part II of our blog series covering the marcus evans 2nd Annual Drug Discovery For Neurodegeneration Conference (see Part I here and Part III here).

We thought that there were some points worth mentioning from a presentation entitled: Translational AD Drug Discovery and Development: The Potential Role of In Vivo Multi-modal Imaging Techniques (yes, it is a mouthful), presented by Dr. Feng Luo of Abbott Laboratories.

Dr. Luo started off by reminding the audience of the recent dismal track record of developing treatments targeting neurodegenerative diseases. Over the past several years, there has been a 90% attrition rate in drugs for neurodegeneration. Clearly, this high failure rate suggests that the drug development community has a problem. The question is, how do we fix it?

Dr. Luo started off his presentation by telling the audience that he and his colleagues at Abbott Labs believe that one of the keys to more effective drug development is finding better biomarkers and creating more relevant “translatable” preclinical studies. They are specifically interested in answering the question “How could we incorporate biomarkers into early [i.e. preclinical] phases of drug development to increase R&D efficiency?” He went on to explain that the approach they are most interested in is the development of more reliable animal imaging tools. In pursuing this approach, they are adapting the most widely-used human imaging (PET, MRI) methods for mice. As a test of this, they sought to characterize one of the most widely-used mouse models of Alzheimer’s Disease (AD), the Tg2576 mouse.

It has long been observed that the human Alzheimer’s brain shows lowered energy usage (hypometabolism). Luo’s group was interested in exploring whether this hypometabolism could serve as a preclinical biomarker; however, no one had ever looked to see whether the Tg2576 mice display this feature of AD. Using three different imaging methods (FDG-PET, fMRI, and MRS) Luo and his group analyzed brain metabolism of the Tg2576 mouse over time. They were shocked to find that 7 month old Tg2576 mice, the age in which animals normally begin to display Alzheimer’s symptoms, not only failed to show decreased brain metabolism, but were instead hypermetabolic (meaning rather than using less energy, the brains of these mice were using more energy)!

As these studies showed, the Tg2576 mouse does not model all aspects of the disease in humans, suggesting that the Tg2576 mouse model may be of limited use in the development of imaging-based disease biomarkers for AD. As Dr. Luo noted in his presentation, animal models are often poorly characterized from a translational perspective. If we are to be able to assess the true utility of any potential therapy, it is critical to show that the therapy acts at its intended target early in the discovery and development process.

This finding in the AD model calls attention to the critical importance of careful characterization of animal models used to research other neurodegenerative diseases such as ALS. While it is generally accepted in the medical research community that there is no perfect animal model for any human disease (meaning disease in an animal will never perfectly mimic disease in a human), developing a detailed description and understanding of all relevant aspects of a given animal model enables researchers to understand the limitations inherent to any particular model so that results can be properly interpreted. The availability and use of multiple animal models for pre-clinical testing increases the probability of finding a drug that will translate to humans.

Although imperfect, animal models have long served as valuable drug development tools, leading to FDA approval of multiple important drugs now widely and safely used in humans. Fortunately for those interested in breakthroughs in ALS therapeutics, extensive characterization of the SOD1 mouse model by researchers at ALS TDI and many other institutions have enabled better and more interpretable studies using this valuable drug development tool. ALS TDI recently announced that extensive characterization of the new TDP-43 mouse model of ALS is also underway (http://quest.mda.org/news/als-tdi-full-speed-ahead).