A birdbrain path to potential Huntington’s Disease therapy

Canary image: Wikimedia Commons

A team at the University of Rochester has succeeded in getting the brain’s native stem cells to replace the nerve cells lost in Huntington’s disease. Their work, published today in Cell Stem Cell dramatically extended the lives of their first set of patients—mice. But they have since replicated the work in monkeys, moving it closer to clinical trials in humans. However, the work began decades ago working with canaries.

After we are born our brains’ stem cells become selective in what cells they will replenish depending on where they reside in the brain. Those in the section of the brain that deals with memory make new neurons. But in the section of the brain that controls muscle function, which is damaged in Huntington’s, the stem cells make new glial cells–the support cells that protect neurons–but not new neurons.

In order to treat Huntington’s, the team had to change the preference of the stem cells in that region of the brain to make neurons instead of glial cells. They did that by manipulating the genes of the stem cells so that they would make more of two proteins. One protein, called BDNF, triggers the stem cells to produce neurons, and the other with a name I love, noggin, suppresses the tendency to produce the glial support cells.

The researchers were able to verify that the stem cells produced new neurons and that those neurons integrated with the rest of the brain. The life expectancy in the mice with a type of Huntington’s doubled in some but not all the animals.

Getting native stem stems to do a better job of repairing and replenishing damaged tissue is a goal of many scientists in the field. But the Rochester team’s path to this very hopeful breakthrough shows the long and critical role of basic research in understanding the normal workings of the body. Much of the knowledge of how to do the current research came from decades of studying canaries and their ability to create new neurons when they learn a new song.

A press release from the university quoted the lead researcher, Steve Goldman, on this work:

“Our work with canaries essentially provided us with the information we needed to understand how to add new neurons to adult brain tissue. Once we mastered how this happened in birds, we set about how to replicate the process in the adult mammalian brain.”

CIRM funds a team at UC Davis using donor stem cells also modified to over produce the protein BDNF to try to rescue or replenish neurons in Huntington’s. That team hopes to complete an early phase clinical trial within the next four years. Here is lead researcher Vicki Wheelock giving a short description of that work:

There are more videos describing stem cell research for Huntington’s disease on our website, along with information about awards we fund for the disease.

DG

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