Targeting Huntington's Disease Mechanisms Early

Research Brief

Targeting Huntington's Disease Mechanisms Early

Cuerpo

The human brain contains some 100 billion so-called interneurons, that transfer signals between sensory and motor neurons and regulate their firing properties and formation of neural networks. Deficits in cortical interneurons have been detected in people with the inherited neurodegenerative disorder Huntington’s disease (HD), but their role in HD development has not been investigated.

Mark F. Mehler, M.D., has received a five-year, $3.4 million National Institutes of Health grant to test whether preventing interneuron deficits from causing adverse effects will ameliorate HD severity or even prevent the disease from occurring. Using a mouse model of Huntington's disease, Dr. Mehler and colleagues will use innovative advanced cell-transplantation techniques to see if they can restore impaired brain function during early stages of the disease.

People with HD inherit a mutation in the gene coding for the huntingtin protein—a defect that causes the DNA trinucleotides C-A-G and C-A-A to repeat many times more than normal causing genome instability. Using postmortem brain tissue from HD patients, the researchers will also investigate whether trinucleotide-repeat length and other DNA modifications in genes coding for DNA repair enzymes influence the severity of interneuron deficits and impairs their function during the critical early developmental period when neural networks are forming. The study’s results may reveal an early-stage therapeutic “window” for preventing the onset and progression of Huntington’s disease, for which there are no effective therapies.

Dr. Mehler is professor and chair of the Saul R. Korey Department of Neurology at Einstein and Montefiore, professor in the Dominick P. Purpura Department of Neuroscience, and of psychiatry and behavioral sciences, director of the Institute for Brain Disorders and Neural Regeneration, and the Alpern Family Foundation Chair in Cerebral Palsy Research at Einstein. (1R01NS125260-01A1)