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Neural Systems: Dynamic Mechanisms Involved in CNS Regeneration and Degeneration

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Ole Isacson, M.D., Ph.D. [Biosketch]
Penelope Hallett, Ph.D.
Jan Pruszak, MD
Arnar Astradsson, MD
Michela Deleidi, MD
Gunnar Hargus, MD, Ph.D.
Jesse McLean, Ph.D.
Teresia Osborn, Ph.D.
Ling Lin, MD, Ph.D.
Ángel Viñuela, MD, Ph.D.
Oliver Cooper, Ph.D.
Jack McDowell
wpe5.jpg (1194 bytes) Neuroregeneration Laboratories,
Program in Neuroscience,
Harvard Medical School
McLean Hospital and Massachusetts General Hospital
The Morris K. Udall Center for Excellence in Parkinson’s Research at Harvard University / McLean Hospital

This program focuses on the mechanisms and dynamics of neuronal regeneration, degeneration and protection with particular emphasis on the neurodegenerative disorders like Parkinson's, Huntington's, and Alzheimer's . Our understanding of regeneration and plasticity of the mammalian nervous system has developed greatly over the last decade, due to basic research in rats following implantation of fetal, cultured or genetically engineered cells into the adult brain . While the adult brain previously was thought of as a non-regenerative system for pathway formation, recent studies show how dissociated primordial neurons implanted into the adult central nervous system can grow to reconnect neuronal pathways and integrate in a molecular and physiological fashion. Thus, anatomical, neurochemical, molecular and behavioral parameters indicate that reconstructive events can take place also in the degenerated adult brain.

The cellular, physiological and molecular events associated with progressive neuronal death and degeneration in the neurodegenerative diseases are still unknown. We search for causal events involved in maintaining neuronal plasticity and health on a cellular level, by (a); constructing model systems that as closely as possible simulate the regional and cellular degeneration seen in brains with neurodegenerative disease, and (b); testing various factors and conditions that may prevent or reverse degeneration in such models. These studies combined are likely to yield to a better understanding of regeneration, development and plasticity of the brain both at a cellular and system integration level. In addition, our research may lead to future therapies for neurodegenerative disease.

Key words: Parkinson's, Huntington's, Alzheimer's, Treatments, Neural transplants, Neuroprotection, Gene Therapy, Animal models.

Project Sites: Neuroregeneration Lab., Dept. of Neurology and Program of Neuroscience, Harvard Medical School, McLean Hospital/Massachusetts General Hospital (Dr. Ole Isacson). Harvard Medical School, New England Regional Primate Research Center, (Dr. Roger Spealman). Massachusetts General Hospital, Dept. of Radiology, Boston (Dr. Anna-Liisa Brownell). Massachusetts General Hospital, Neurosurgery Research, Boston (Dr. Robert L. Martuza). Massachusetts General Hospital, Neurogenetics Lab., Charlestown (Dr. Xandra O. Breakefield). Neurological Associates, Sarasota Florida  (Dr Jim Schumacher), Brain Repair Centre, Dalhousie University, Halifax, Nova Scotia (Dr. Ivar Mendez).

Program Director: Dr. Ole Isacson , McLean Hospital, Neuroregeneration Laboratory, 115 Mill Street, Belmont, MA 02178. Contact Person, Dr. Ole Isacson, Director, Telephone: (617) 855-3243, FAX: (617) 855-3284, E-Mail: - [Biosketch]

Training Opportunities: Currently there are 5 post-doctoral fellows and 2 graduate students. There is a possibility of openings for other trainees at the pre and postdoctoral level if funds are made available.

Representative Publications:

  1. Isacson, O. (1995) On behavioral effects and gene delivery in Parkinson's rat model. Science, 269, 856-857.
  2. Isacson, O., Deacon, T.W., Pakzaban, P., Galpern, W.R., Dinsmore, J., and Burns, L.H. (1995) Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres. Nature Med. 1, 1189-1194.
  3. Mendez I, Vinuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski JQ, Isacson O. (2008) Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat Med;14:507-9.
  4. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R. (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136, 964-977.
  5. Chung, CY, Koprich JB, Hallett PJ, Isacson O. (2009) Functional enhancement and protection of dopaminergic terminals
    by RAB3B overexpression. Proc Natl Acad Sci USA 106:22474-79.
For a video on the transplantation of fetal pig cells into people with neurodegenerative diseases click here. [1.1 Mb .mov format, courtesy of ABC News]
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