Immune Pathway to Slow Huntington Disease

Huntington disease is a rare, inherited neurodegenerative disorder caused by a mutation in the huntingtin gene. It leads to progressive loss of nerve cells in the brain, resulting in worsening problems with movement, thinking and behavior. The disease is ultimately fatal, and while current treatments can ease symptoms, there are no therapies that slow or stop its progression. Increasing evidence suggests that chronic inflammation in the brain plays a major role in driving disease progression.

In a new study from Florida Atlantic University and collaborators, researchers identified the immune cGAS-STING pathway as a key contributor to this harmful inflammation. Using a humanized mouse model of Huntington disease, they found that blocking this pathway – either by removing the cGAS gene or using a drug that inhibits STING – reduced brain inflammation, protected neurons and improved motor function. The findings suggest that targeting cGAS-STING could offer a promising new therapeutic strategy to slow Huntington disease progression.

“Current Huntington disease therapies largely focus on lowering huntingtin protein levels, but many of these approaches are complex, expensive and difficult to scale because they also risk reducing the healthy version of the protein needed for normal brain function,” said Srinivasa Subramaniam, Ph.D., senior author, associate professor in the Department of Chemistry and Biochemistry within FAU’s Charles E. Schmidt College of Science, and a member of FAU’s Stiles-Nicholson Brain Institute, David and Lynn Nicholson Center for Neuroscience Research, and the Center for Molecular Biology and Biotechnology. “Our findings point to a potentially simpler and more accessible strategy: targeting the cGAS-STING inflammatory pathway with small-molecule drugs.”

Read the press release.