|Brain volume is reduced in people with Huntington’s disease. Image: Frank Gaillard, Wikimedia commons|
The deadly neurodegenerative condition Huntington’s disease occurs in people with a mutation in a gene called huntingtin. Scientists have known that since 1993.
The question has been what to do about it. There is currently no therapy to slow or halt the inevitable degeneration of people with the mutation.
Steven Finkbeiner at the Gladstone Institutes recently got a Basic Biology award to better understand what goes wrong in the neurons of people who carry that mutated huntingtin gene. Bernadette Tansey recently wrote in Xconomy about his work and his collaboration with San Bruno-based Numerate, which got one of our Early Translational Awards to find drugs that block whatever is that’s going wrong in those cells.
Tansey described the relationship like this:
Finkbeiner figured out how a region of a mutant protein attacks the nerves of people with Huntington’s, a devastating neurodegenerative disorder that leads to disability and eventual death. Numerate will be looking for drug candidates to block that protein.
She goes on:
Numerate will be searching for a small molecule that prevents the mutant huntingtin protein from folding into a particular structure that, according to Finkbeiner’s research, helps it destroy nerve cells. Once Numerate has identified its best bets, Finkbeiner’s lab will use a second new method that may also revolutionize drug discovery. His lab will first test the drug candidates on human nerve cells grown in a lab dish, rather than in animals that have been engineered to develop a facsimile of Huntington’s disease in humans.
The key point here is that they are going to be testing the drugs in human cells that contain the mutated gene. This is a dramatic difference from older approaches which relied on animals with a facsimile of the disease. The animals don’t have the same disease, the animals aren’t human, and the drugs found to be effective in that system in the past haven’t worked in people.
This is one of a few novel approaches were funding to find a therapy for Huntington’s disease. You can read about the rest, and watch our videos about those approaches, on our Huntington’s disease fact sheet.