In a new research, published in the Journal of Clinical Investigation, scientists at the University of Rochester Medical Center have shown how stem-cell therapy might someday be used to treat Huntington’s disease — a fatal disorder for which there is currently no cure or even a treatment to slow the disease.

The team used gene therapy to guide the development of endogenous stem cells in the brains of mice affected by a form of Huntington’s. The mice that were treated lived significantly longer, were healthier, and had many more new, viable brain cells than their counterparts that did not receive the treatment.

“There isn’t much out there right now for patients who suffer from this utterly devastating disease,” said Steven Goldman, M.D., Ph.D., who is at the forefront developing new techniques to try to bring stem-cell therapy to the bedside of patients. “While the promise of stem cells is broadly discussed for many diseases, it’s actually conditions like Huntington’s — where a very specific type of brain cell in a particular region of the brain is vulnerable — that are most likely to benefit from stem-cell-based therapy.”

The latest results have their roots in research Goldman did more than 20 years ago as a graduate student at Rockefeller University. In basic neuroscience studies, Goldman was investigating how canaries learn new songs, and he found that every time a canary learns a new song, it creates new brain cells called neurons. His doctoral thesis in 1983 was the first report of neurogenesis — the production of new brain cells — in the adult brain, and opened the door to the possibility that the brain has a font of stem cells that could serve as the source for new cells.

“The type of brain cell that allows a canary to learn a new song is the same cell type that dies in patients with Huntington’s disease,” said Goldman, professor of Neurology, Neurosurgery, and Pediatrics, and chief of the Division of Cell and Gene Therapy. “Once we worked out the molecular signals that control the development of these brain cells, the next logical step was to try to trigger their regeneration in Huntington’s disease.”

Stem cells offer a potential pool to replace neurons lost in almost any disease, but first scientists must learn the extensive molecular signaling that shapes their development. The fate of a stem cell depends on scores of biochemical signals — in the brain, a stem cell might become a dopamine-producing neuron, perhaps, or maybe a medium spiny neuron, cells that are destroyed by Parkinson’s and Huntington’s diseases, respectively.

The experiment was designed to test the idea that scientists could generate new medium spiny neurons in an organism where those neurons had already become sick. Now that the capability has been demonstrated, Goldman is working on ways to extend the duration of the improvement. Ultimately he hopes to assess this potential approach to treatment in patients.

“This offers a strategy to restore brain cells that have been lost due to disease. That could perhaps be coupled with other treatments currently under development,” said Goldman. Many of those treatments are being studied at the University, which is home to a Huntington’s Disease Center of Excellence and is the base for the Huntington Study Group.

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