Ole Isacson, M.D.

Director of the Neuroregeneration Research Institute at McLean Hospital, Professor of Neurology at Harvard Medical School; and co-chair of Harvard Center for Neurodegeneration and Repair

At The Stern Center for Neuroregeneration Research at Harvard University’s McLean Hospital, we support the work of Dr. Ole Isacson. Under the direction of Professor Ole Isacson, researchers at Harvard Medical School and McLean Hospital are pursuing PD research on three major fronts: neurotransmitter vesicles, transcription factors, neural stem cell biomarkers.

• Neurotransmitter vesicles. Most PD therapeutic approaches to date are based on enhancing dopaminergic neurotransmission, either through a dopamine “substitute” (e.g., L-DOPA) or by increasing the amount of dopamine itself, e.g., by reducing its presynaptic reuptake or breakdown. The Harvard-McLean researchers have identified another, potentially promising approach: increasing the vesicles (intracellular storage compartments) that store dopamine in presynaptic neurons. Specifically, they showed that genetically overexpressing the vesicle protein RAB3B in animal models of PD maintained functional levels of a dopamine metabolite (DOPAC) for a longer period of time following L-DOPA administration.

Their study is the first to show that synaptic vesicles can be genetically altered and enhanced in an animal model of PD.

• Transcription factors. Transcription factors “transcribe” the information from DNA to RNA, a key step in the synthesis of proteins. One particular transcription factor, Otx2, largely determines the structure and function of the A10-type neurons, which are more protected from damage in PD than another type, A9.Their findings suggest that Otx2 may alter susceptibility to PD because they found that genetic overexpression of Otx2 increased protection of toxic damage from A9. Follow-up studies showed that genetic variations in Otx2 are associated with PD risk and age of onset.
• Stem cell biomarkers. A critical step in developing stem cell therapy involves accurately characterizing and purifying the stem cells to be used. While this has been done with blood (hematopoietic) stem cells using cell surface markers, it has not been done with neural stem cells. This team has achieved an important first step by identifying a number of such markers (CD15, CD24, and CD29) on human embryonic neural cells, and successfully transplanted specific subpopulations in animal models.

Success in this research is likely to result in new drugs capable of slowing PD in its course.