Program Leader: Jeffrey D. Macklis, MD, D.HST

The HSCI Nervous System Diseases Program’s mission is to develop new and effective therapies for diseases of the nervous system, especially those involving the degeneration of or injury to specific cell types. Because the nervous system includes so many distinct types of neurons, glia, and functional circuitries, the program is organized into the following five research groups: motor system disorders (including ALS, spinal cord injury, Huntington’s disease, forms of cerebral palsy, and stroke); Parkinson’s disease; retinal disease; hearing disorders; and glial-based disorders (including multiple sclerosis and forms of cerebral palsy).

Each of these groups is trying to answer three key questions:

• Do adult stem cells that have the ability to differentiate into the key types of neurons or glia exist within the nervous system?
• What key molecules and genes control the extremely precise differentiation of these cells?
• Can such adult progenitors and/or embryonic stem cells be directed to differentiate into cells that can be used to replace diseased or injured cells—either by local progenitors in the tissue or by cells grown in the laboratory?

 
Key research findings in the past year include:

• New control genes have been identified that may be critical for nervous system stem cells to define themselves and differentiate into the specific neurons that die in ALS and are injured in spinal cord injury
• Key candidate control molecules in “corticospinal motor neurons” were investigated, and it was discovered that these neurons, central to the diagnosis and morbidity of classic human ALS, degenerate quite early in the most commonly studied transgenic mouse model of familial ALS
• Chemical screening has begun for agents that activate oligodendrocyte progenitors to a remyelinating state, potentially beneficial in both MS and demyelinating forms of cerebral palsy

Technology Advancements

New genetically engineered mouse lines are being produced to aid the investigation of specific adult progenitors in the brains of young and adult mice that appear to have the ability to produce replacement neurons for ALS and spinal cord injury.

In another important technological advancement, the ability to create specific nervous system cell types from hESCs has made it possible to achieve both the quality and quantity of cells needed to conduct therapeutic screening in search of small molecules, compounds, gene products, and proteins that could be turned into diverse therapeutics for diseases. At HSCI’s Therapeutic Screening Center, headed by Lee Rubin, PhD, Director of Translational Medicine at HSCI, researchers are using this technology to search for treatments for orphan nervous system diseases.

Sparking Collaborations

Annual think tanks have been an incredible success and benefit not only the Nervous System Diseases Program but also the international research community. Each year, HSCI assembles world leaders in nervous system disease research to combine their expertise on a specific topic with the objective of identifying key areas of focus for the field and developing collaborative research projects. Throughout the year, monthly program inter-lab meetings, where faculty, postdocs, and students from across different labs present work-in-progress for critical evaluation and advice, have also proven highly valuable to the community as a whole.