MAR 19, 2014 09:00 AM PDT

Remyelinating the adult central nervous system: Repairing injury in MS

Presented At Neuroscience
  • Director of UCSF Neurodiagnostics Center, Director of UCSF Multiple Sclerosis Center, Rachleff Endowed Professor, Associate Professor of Neurology and Opthalmology, UCSF School of Medicine
      Dr. Ari J. Green is Clinical Director of the UCSF Multiple Sclerosis (MS) Center and director of the UCSF Neurodiagnostics Center. He treats adults and children with MS and other inflammatory diseases of the central nervous system and has expertise in treating visual problems resulting from these conditions. In his research, he addresses how MS affects the visual system and methods to track and predict the course of the disease. He also uses advanced retinal imaging and electrophysiology to investigate the retina and optic nerve and the relationships between inflammation, demyelination and neurodegeneration in the disease and to better understand injury to nerve fibers of the brain in MS.
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      <br />Green earned a medical degree at Duke University School of Medicine in Durham, N.C., and completed an internal medicine internship in 2002 and neurology residency in 2005, both at UCSF. In 2005, he was chief resident at UCSF. He completed neuro-immunology and neuro-ophthalmology fellowships at UCSF and has won several awards including a Howard Hughes Medical Institute Early Career Scientist Award and a clinician-scientist award from the National Multiple Sclerosis Society and American Academy of Neurology Foundation. Green is an associate professor of Neurology and Opthalmology at UCSF.
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    Multiple Sclerosis is a debilitating neurodegnerative disease of the central nervous system in which the immune system targets and destroys myelin sheaths surrounding axons. Progressive and permanent neurological disability in the disease is caused by the ultimate loss of the underlying axons themselves. Nearly a dozen FDA-approved therapies exist to help reduce the inflammation that contributes to immune mediated injury or prevent the influx of immune cells from peripheral circulation into the CNS. However, to date there are no therapies capable of protecting axon loss and/or regenerating lost myelin. There are compelling reasons to think that maintenance or restoration of myelin integrity would help with protection of axons from loss and injury. Myelin in the CNS is an extension of the plasma membrane from mature oligodendrocytes - a specialized cell type whose principal purpose is to provide the myelin needed to ensheath axons. The precursor cell for oligodendrocytes known as OPCs are tiled throughout the CNS, but they don't appear to adequately differentiate into mature oligodendrocytes capable of restoring myelination to denuded axons. This talk will discuss the use of a novel high throughput screen for the identification of small molecules with the capacity to induce oligodendrocyte differentiation and myelin wrapping. It will also discuss the validation of the "hits" from this screening assay and the rapid introduction of these therapeutic targets to patients including the selection of targets focusing on mechanism of action and BBB penetration. This will include discussion of the importance of development of clinical trial outcomes for the advancement of successful therapeutic programs in neuroprotection.

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