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Ole Isacson, M.D., leads the Udall Center at Harvard University Medical School and McLean Hospital in Belmont, Massachusetts. His team studies several novel treatments for Parkinson's disease in animal models. One project evaluates the ability of a new compound with neuroprotective properties to prevent and reverse parkinsonism in primates. Another project expands on tissue implantation research. Previous implantation investigations have been limited to single transplants into the part of the brain called the striatum. Dr. Isacson's group uses a primate model to examine the effect of multiple fetal or stem cell implants into the striatum and the substantia nigra and subthalamic nucleus, other areas of the brain that are affected by the dopamine loss characteristic of Parkinson's disease. They also transplant embryonic mouse tissue into rodent and primate Parkinson's models. Behavioral measurements, imaging studies using PET and magnetic resonance spectroscopy, and post-mortem tissue studies are used to evaluate the efficacy of the therapies. Benefits seen in any of these animal studies could lead to clinical trials in humans with Parkinson's disease.
There are compelling research opportunities for Parkinson's Disease (PD) therapies. While L-dopa provides initial relief, there is a need for alternative strategies to deal with the continued loss of dopaminergic (DA) neurons, axons and terminals. We have a functional collaborative scientific group centered at McLean Hospital and Harvard Primate Center that investigates neuroprotective, neuromodulatory and cell therapy approaches for PD. We use animal models, including MPTP-treated animals with loss of dopamine cells, synapses and function. This Center is organized with 3 Cores that serve this and other NIH PD Centers, and 3 specific Projects that explore the shared theme of "Novel Therapeutic Approaches for Parkinson's Disease".
The Harvard University/McLean Hospital Udall Parkinson's Disease Research Center of Excellence:
Project 1. Functional differences between dopamine (DA) neurons in the substantia nigra (A9) that are vulnerable to PD compared to those spared in the same midbrain tissue region A10 (VTA) are examined. We discovered new gene and molecular candidates for neuroprotection by specific laser-capture and genomic analysis of characteristic DA neurons, now tested systematically by tissue culture and animal models to identify new pathways and substances providing insights into the pathogeneses and novel therapies for PD. Project 1 links to NIH Udall Centers, including specific collaborations with Duke U Udall Center for genomic convergence analysis of PD susceptibility genes from bioinformatics, linkage analysis and finally functional tests in our PD model systems.
Project 2. Post-mitotic but immature DA neurons are derived from primate and human stem cells for restorative transplantation into sophisticated PD model primates (including functional tests and imaging - see Core B). Project 2 works with collaborators and NIH Udall Centers, and like Project 1 and 3 is internally served by Core A, B and C, and specifically by its transplantation in PD primate models linked to the supply of genetically engineered human stem cells produced in Project 3.
Project 3. Specific midbrain genes and transcription factors controlling DA neuron development are identified and engineered into mouse and human stem cells. The resulting DA neurons are tested for functional repair in PD models in collaborative experiments in the Center. By using combinations of factors, a large fraction of stem cell derived cultured TH-positive GFP labeled and midbrain mouse or human neurons are sorted for purity and safety by the Center's advanced FACS technology before transplantation.
This PD Center also provides significant PD research education and training for scientists, and service to the PD patient and medical research communities. The Center's 3 research projects and its integrated Administrative Core (Core A), Functional Imaging Core (Core B) and a Clinical Transplantation, Bioinformatics, Human and Stem Cell Marker Core (Core C) are unique components in the NIH Udall Center of Excellence Consortium. The Harvard-McLean NIH Parkinson's Disease Research Center of Excellence provides a specialized environment for synergistic PD research on stem cell derived therapies, novel insights into functional genetic analysis of vulnerability of midbrain DA neurons and cutting edge research of new modalities leading to novel treatments for PD patients.
PUBLICATIONS FROM PD CENTER GRANT WORK: (1999-2006, 7 years)
Contact Information or Udall Center Link:
Harvard University/McLean Hospital Udall Center website
Last updated August 13, 2007