Wednesday, May 19, 2010

Drug Development for Neurodegenerative Diseases Conference Part 1

Prize4Life is pleased to bring you exclusive coverage as the conference blogger for Drug Development for Neurodegenerative Diseases, a conference organized by marcus evans. With over 40 representatives from industry and academia, the conference is focused on new therapeutic developments, biomarkers, target identification, and issues in clinical trial design for neurodegenerative disease. Without further adieu we bring you the round-up from day one….

The first set of sessions focused on current updates in therapy development for neurodegenerative treatment.

First up was a joint presentation entitled: Protein Kinase C: A Basis for Biomarkers and Therapeutics for Alzheimer’s Disease co-presented by Drs. C. Anthony Altar and Daniel Alkon of the Blanchette Rockefeller Neuroscience Institute.

This first set of presentations focused on a signaling pathway that may serve as a new target for Alzheimer’s Disease (AD) and eventually other neurodegenerative conditions. A key deficit common across neurodegenerative disease is the loss of synapses, the contact and communication point between cells of the nervous system. Activation of the molecule Protein Kinase C-epsilon appears to mitigate and potentially even reverse synapse loss.

As the presenters explained, dramatic pathologic changes like plaques and tangles are late events in Alzheimer’s, “tombstones rather than precursors”. Early events, like the loss of synapses (a process that occurs well before formation of the famous plaques and tangles we usually hear about), correlate well with a given individual’s degree of dementia, but plaques and tangles don’t. Given that memory loss is the hallmark of AD, the presenters were interested in gaining a better understanding of the molecular changes that store memory: changes in the synapse.

Dr. Tony Altar, the former director of The Biomarkers Consortium for the Foundation for the National Institutes of Health, and the current Director of the Alzheimer’s Diagnostic Laboratory of the Blanchette Rockefeller Neurosciences Institute, spoke first.

He presented recent data indicating that defects in PKC-epsilon signaling can be sensitively detected in cultured skin cells called fibroblasts. Moreover, he showed that the PKC-epsilon pathway defects seen in cultured fibroblasts from AD patients were similar to those found in postmortem AD brain tissue. The implication is that these easily accessible fibroblast cells can be used to potentially diagnose and screen treatments for Alzheimer’s Disease (and potentially other neurodegenerative diseases). Using fibroblasts from both patients with presumed AD and control patients without the disease, Dr. Altar showed that his lab could use fibroblasts to distinguish these two populations with a high degree of sensitivity and specificity.

In future studies his group hopes to further refine the system so as to provide early diagnosis of AD and discriminate AD from other forms of dementia, thereby allowing better stratification of patients for therapeutic trials and treatments.

In a companion presentation, Dr. Daniel Alkon, Scientific Director of the Blanchette Rockefeller Neurosciences Institute, delved into how his group was using knowledge of the PKC-epsilon pathway to develop potentially novel AD treatments.

PKC-epsilon is a form of Protein Kinase C found almost exclusively in the brain. Dr. Alkon’s group has identified a class of compounds that can activate PKC-epsilon without any obvious toxicity and with good blood brain barrier penetrance, ideal qualities for a drug to treat diseases of the brain!

Their lead compound, bryostatin, is able to prevent and reverse the damage seen in the brains of a variety of different models of AD transgenic mice. Intriguingly, bryostatin has also been shown to induce synapse formation in an animal model of Fragile X, a disease in which animals are born missing many synapses, suggesting that this drug may be efficacious even when administered late in AD disease progression after significant synaptic loss has already occurred.

Dr. Alkon is now preparing for an FDA-approved phase II trial of bryostatin (which had previously been shown to be safe in a large cancer trial). Our reporter probed as to whether these researchers would consider testing bryostatin in motor neurons and/or ALS mouse models and was pleased to hear a yes! This identification of the critical role of certain members of the Protein Kinase C family in synapse formation and maintenance holds potential implications for all diseases and disorders in which neuronal cell communication is disrupted. A promising avenue of discovery Prize4Life will continue to track closely.

Wednesday, May 12, 2010

Untangling ALS: A Conversation with Dr. Richard Bedlock on Off-Label ALS Therapies

60-Minutes recently did a full length feature entitled “21st-Century Snake Oil: 60-minutes cameras expose con men who prey on dying victims”, discussing the dangers of untested off-label therapies that have been pushed by non-medical doctors.

“Today, quack medicine has never been bigger. In the 21st century, snake oil has been replaced by bogus therapies using stem cells. Stem cells may offer cures one day, but medical charlatans on the Internet are making outrageous claims that they can reverse the incurable,” reports CBS. The piece highlighted the case of Lawrence Stowe, a so-called stem cell doctor whose ‘clinic’, based in Mexico, alleged to cure patients of their ALS. Credible ALS researchers dismiss Lawrence Stowe’s claims as baseless.

Yet, every year, patients are taken in by incredible claims such as Stowe’s, often losing hundreds of thousands of dollars in the process.

ALS clinicians worry about the preponderance of these shams, and Dr. Richard Bedlack is at the forefront of efforts to ensure that patients have credible, scientifically-supported information to inform their decisions. Prize4Life was pleased to have the opportunity to speak with Dr. Bedlack, Director of the Duke University MDA/ALS clinic.

Dr. Bedlack is a member of the ALS Research Group (ALSRG), and a founder of two related ALSRG initiatives to promote patient safety and information: ALSuntangled, a Twitter feed, wherein ALS patients can ask questions and receive answers about off-label or alternative ALS Therapies (you can follow the feed at and a founder and moderator of a social community (see it as a NING site) that is dedicated to discussing the safety and efficacy of off-label ALS treatments (known as AOTs).

Dr. Bedlack spoke with Meghan Kallman, Prize4Life’s Marketing & Communications Manager.

MK: Thank you for being with us. To start off, why do you think there is so much confusion surrounding off-label ALS treatments?

RB: The internet has created an amazing opportunity for connecting sellers and buyers, whether it be for antique cars or for treatments for incurable diseases. Unfortunately, while the breadth of all this information is astonishing, there is often little depth. There are usually no “internet police” to check sellers’ facts. Add to this the desperation of patients with ALS (which may lower their skepticism some), and it is easy to see a recipe for potential disaster.

MK: What is the ALS Research Group? What do you do that differentiates you from other research collaborations?

RB: The ALS Research Group (ALSRG, is comprised of more than 100 ALS Clinician-Scientists from across North America. It was established in 2003 with the purpose of improving ALS patient care, research and education. Most research collaborations are designed around clinical trials. The ALSRG is broader in scope and more interested in infrastructure for patient care, research and education.

MK: The ALS Research Group, ALSUntangled, and the NING site are all related in that they help ALS patients make sense of competing information about alternative therapies. Why did you find alternative off-label therapies in the context of ALS concerning?

RB: ALSUntangled is just one of many current ALSRG projects. The goal of ALSUntangled is to use social networking to bring patients, clinicians and scientists together for examining alternative and off-label ALS treatments (AOTs).
Patients who want to use ALSUntangled can ask about AOTs via twitter or email. Specific AOTs that patients ask about are brought into an invitation-only part of the web called NING, where they are discussed among invited, accomplished ALS clinicians and scientists. Finally, a summary of the discussion with a consensus conclusion is published via free access in each issue of the ALS Journal (see for further details).

A major focus of several current ALSRG projects is to improve enrollment in ALS research studies. A survey of ALSRG investigators suggested that one reason patients decline enrollment in a research study is to pursue AOTs (see Amyotrophic Lateral Sclerosis 2008, Vol. 9, No. 5: Pages 257-265). Unfortunately, we have found that the evidence presented for the cost, efficacy and safety of AOTs is often either scant or inaccurate (Amyotrophic Lateral Sclerosis. 2009 Jun; 10(3):182-4.). Thus, we decided to form ALSUntangled to help patients better understand AOTs and make more informed decisions.

It is clear that not all AOTs, nor their proponents, are the same. When ALSUntangled goes into an investigation of a particular AOT or clinic, it does so with an open mind. Some of these therapies are being offered by proponents who genuinely believe they have something that works for ALS. Others are being offered by con men. Our goal is to not to discover the proponent’s motivation, but simply to clarify the AOT’s cost, rationale, evidence for safety and evidence for efficacy.

MK: What is the NING site? Why was it developed?

The NING is just one part of ALSUntangled. The NING site is only for invited ALS clinicians and scientists, and is used for us to privately discuss the AOTs that we are asked about. We then to come to a consensus for our publications. We wanted a site like this so that we could be sure about the credentials and motivation of those weighing in, and so we could be free to discuss each AOT without having to worry that any of us would be personally attacked because of our individual opinion.

Did you find that ALS experts were willing to participate in NING and ALSUntangled? Did you encounter particular enthusiasm or particular resistance?

RB: We currently have 66 experts from across 5 different countries participating in ALSUntangled. Those experts are also registered and active in the NING portion of the project. While most of my fellow members of the ALSRG are enthusiastic and excited about this program, it does appear that the social networking technology may be a barrier for some. We are thus building a new website which will have a forum section whereby patients and experts can even more easily discuss AOTs.

MK: Have ALS patients been using ALSUntangled? How has it been received?

RB: Now just one year old, we currently have 160 followers on Twitter, and many more patients reading our free online investigations. The project appears to be well received, and we look forward to growing in popularity and utilization when we launch our new website later this year.

MK: Why did you choose social media as an outlet for ALSUntangled? Have there been tools that you have found particularly useful?

RB: While social media such as twitter and NING are used most commonly for recreation, they are incredibly powerful tools for bringing people from widely different geographies and backgrounds together for a common purpose.

MK: What have been the results of some of the NING investigations, in addition to providing a forum for clinicians? Has the group published anything?

RB: We have published investigations on Lyme Disease, Iplex, the Hickey Wellness Center, Stem Cell Transplants at Hospital San Jose Tecnologico de Monterrey, and the XCell-Center. These can be found in the ALS Journal or on various websites (see, for example

MK: Why do you think that shams such as Lawrence Stowe’s ‘clinic’ in Mexico (featured on 60 Minutes) continue to be successful?

RB: If I did not have a scientific background, and my wife had just been diagnosed with ALS, the claims of sellers like Stowe would be awfully tempting. Again, this terrible disease really makes people vulnerable.

MK: What is the ALS clinical community doing to counteract these sorts of problems with ‘snake oil’ salesmen?

RB: Individual ALS clinicians have long fielded questions from patients about AOTs. For years they had to try and investigate these questions on their own. ALSUntangled tries to make this process easier and much more powerful. Once we publish an investigation, future internet searches of that AOT should yield not only the original advertisement for it, but also our detailed critique. Patients can then make a more informed decision as to whether they wish to pursue the AOT.

MK: Do you have any observations on how to help ALS patients avoid this kind of fraud? Are there good ways to know when the science is legitimate? What can ALS patients do to protect themselves?

Patients with ALS should always discuss any AOT they are considering with their doctor and/or an ALS expert. There are some definite red flags suggesting that a particular AOT probably should be avoided. These include a large up-front cost, use in multiple diseases with diverse causes (example: a treatment that claims to work in ALS, MS, PD, stroke, fibromyalgia, cerebral palsy), the use of case reports as evidence of effectiveness, and lack of any safety data. ALSUntangled is here to help!

We encourage ALS patients and caregivers to make extensive use of ALSuntangled. Thanks very much to Dr. Bedlack and his colleagues for creating such a valuable resource!

Tune in next Tuesday and Wednesday as we bring you live coverage of the marcus evans Second Annual Drug Development for Neurodegenerative Diseases Conference, from May 19-20 in Boston, MA. Prize4Life will be blogging live on the conference, which will feature speeches from industry professionals and leading pharmaceutical and biopharma companies. Presenters will discuss innovation in clinical studies, clinical trial designs, biomarker discoveries and drug discovery for neurodegenerative disease. To learn more or register, click here.