Partners will look for genes related to onset and progression as well as drug targets.

The Institute for Systems Biology (ISB) is collaborating with the Gladstone Institute of Neurological Disease (GIND) and its Taube-Koret Center for Huntington’s Disease Research. They will use whole-genome sequencing to identify genes and novel drug targets related to the onset and progression of Huntington disease (HD). The research team, led by GIND associate director and senior investigator Steven Finkbeiner, M.D., Ph.D., will also use induced pluripotent stem cells (iPSCs) from patients with HD to screen for drugs that might delay, prevent, or even reverse the condition.

The Gladstone team will provide DNA samples of HD patients and family members who are unaffected or at risk for HD. The samples will be sequenced by ISB in partnership with Complete Genomics.

“This is the first disease-focused project that will use the power of whole-genome sequencing in families,” according to David Galas, ISB’s svp for strategic partnerships. “With Gladstone’s deep experience in Huntington’s disease and in stem cell biology, we can make a tremendous step toward finding strategies for a cure.”

HD is an inherited degenerative brain disorder attributed to a single gene mutation. However, Dr. Finkbeiner, who directs the Taube-Koret Center for Huntington’s Disease Research, says that other genes may regulate the onset and progression of the disease and influence the particular symptoms that each individual experiences. “We hope to find out why HD manifests and progresses in different ways in different people and to discover other genes that influence the disease.”

ISB’s president, Lee Hood, M.D., Ph.D., comments “ISB has already demonstrated the power of using whole family genome sequencing to identify genes that encode simple genetic diseases. This study offers the opportunity to go one step further and actually find genes that modify the effects of a well-known disease gene.”

Taube-Koret Center investigators are part of a NIH-funded consortium that uses iPSCs to develop human neurons with HD characteristics. Fibroblasts are obtained from skin cells of HD patients and converted first into iPSCs and then into neurons that may provide a more accurate platform for testing new therapies than currently available experimental models.

“One of the challenges of Huntington and many other neurological diseases is that many potential therapies that show promise in animal models turn out to be ineffective in people,” Dr. Finkbeiner notes. “One of the promises of iPSC technology is to be able to develop models from HD patients that can give us more detailed information about the disease and better predict how therapies could work in humans.”

He pointed out that genomic information from the new collaboration could expand therapeutic opportunities not only for HD but also for other neurological diseases. “The hope is that the work we do here will lay the foundation for applying these techniques to more common but unfortunately more complex neurodegenerative diseases,” Dr. Finkbeiner says.

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