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.