Program Leader: Jeffrey D. Macklis, MD

Background

Neurodegenerative diseases are poorly understood. Although expert neurologists can often identify many of their cardinal features at a symptom, pathology, and imaging level, and thus know some elements of which neurons, circuits and systems are involved, in many cases far too little is actually known that could contribute toward developing new therapies.
Neurodegenerative diseases are defined as hereditary and sporadic conditions which are characterized by progressive loss of structure or function of neurons that may lead to neuronal death. For example, population aging has caused an epidemic of dementia which is set to worsen in the coming years. In the US Alzheimer's disease alone affects 5 million people. While the human cost is incalculable, the financial burden of caring for these patients is now $150 billion a year. Close to half of us will have Alzheimer's by the time we reach the age of 85. Another example is spinal cord injury which affects 250,000 Americans with approximately 11,000 new injuries each year. Athough we are beginning to understand the causes of these and other such illnesses, there have been few advances in treating them.

Focus

The HSCI Nervous System Program focuses on neurodegenerative and traumatic diseases of the brain and spinal cord. In particular this collaborative, inter-institutional research program studies Amyotrophic Lateral Sclerosis (ALS), often referred to as "Lou Gehrig's Disease”; spinal cord injury; Alzheimer’s disease; narcolepsy, and- by extension- corticobasal degeneration; Huntington's disease and Parkinson’s disease. The aim is to understand exactly which neurons degenerate and why, and how to interfere with the degenerative process.

Sample Projects

HSCI investigators have developed many areas of complementary expertise that come together to pursue the developmental biology of stem cells and related neurobiology relevant to attaining a deeper mechanistic understanding of neurodegenerative diseases and the application of the science to therapies. In particular, the group is moving in two directions. The first one is pursuing stem cell therapy by directing the differentiation of adult progenitors and/or embryonic stem cells into the specific types of neurons (e.g. cortico-spinal motor neurons, hypocretin neurons, corticofugal neurons) that can replace diseased or injured cells in the different neurological diseases. The second involves screening for chemicals that direct the differentiation of desired cells among the many types of neurons as well as for chemicals that could be used therapeutically in neurodegenerative diseases.

Another exciting project is a pre-clinical study that involves the transplantation of dopamine neurons differentiated from an individual's own iPS cells in the midbrain. This will be the first trial ever to test if neurons derived from iPS cells can create functional recovery in primates, which obviously would provide a very important step before any potential application of human iPS cells.

Extending the Program

Over the past few years the Nervous System Program has funded projects in multiple laboratories and has built a community of stem cell scientists that regularly come together throughout the year in lab and program meetings for productive exchanges of information and ideas. The program has also pioneered the concept of the Program Think Tank, a model which is now being followed by the other disease programs within HSCI.  The Think Tank is an annual meeting of local investigators to which distinguished international scientists are invited and is an opportunity to discuss the latest experimental results, share data and develop new ideas with the best scientists from around the world. This type of collegial collaboration is invaluable and essential to move science in this field and in the broader stem cell field forward faster.