Hamdan Medical Journal (previously the Journal of Medical Sciences)

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The Genetic Research Cycle in Human Disease: The Huntington's Disease Paradigm

James F Gusella
Published in : Journal of Medical Sciences ; Vol 2, No 1 (2009)
DOI : 10.2174/1996327000902010029


For more than a century after the description of Huntington's Disease (HD), an inherited neurodegenerative disorder, by George Huntington, a physician on Long Island New York, research into the affliction concentrated on clinical and neuropathological correlates, trying to work backwards from these phenotypes to crucial steps earlier in the disease pathway. These efforts provided excellent clinical and pathological descriptions, and supplied chemical models in rodents, but working backwards from the ultimate disease phenotype did not identify definitive, causative biochemical steps in the disease process or provide a rational route to an effective therapy. In 1983, an alternative approach emerged, aimed at studying pathogenesis from its starting point, the HD gene, rather than from its endpoint, neuronal dysfunction and loss. This paradigm, which I term the Genetic Research Cycle, has acted as a model for similar investigations in a wide range of neurological disorders, leading to better diagnosis and patient management, deeper understanding of pathogenesis, and routes for developing rational, effective treatments.

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