Spinocerebellar ataxia type 6 (SCA6), a rare neurodegenerative disorder, is characterized by severe, progressive movement and balance issues. It is associated with low levels of a neural molecule called brain-derived neurotrophic factor (BDNF), which guides the growth and maintenance of brain cells and overall plasticity. SCA6 affects one in 100,000 people worldwide. Research has shown that exercise can significantly restore BDNF levels in SCA6 patients, but some SCA6 patients have such limited movement that they cannot exercise.
Along with her lab, Alanna Watt, a professor in McGill’s Department of Biology, has identified a new drug that mimics the effects of exercise on BDNF levels, opening the door to more accessible treatment for patients with SCA6. The team’s findings were published in Science.
In an email to The McGill Tribune, Anna Cook, a PhD candidate in Watt’s lab and first author of the paper, explained that finding new ways to exercise was the main driver for SCA6-related therapy research.
“Exercise is a low-cost intervention that is accessible to SCA6 patients all over the world, even to those without access to healthcare,” Cook said. “However, exercise as a treatment has its own problems, particularly in people with movement disorders who might find it difficult to exercise. That’s why we wanted to build on finding drugs that work in the same way.”
Low levels of BDNF are also seen in patients with Parkinson’s and Alzheimer’s. Cook’s research began with her finding that the expression of BDNF and its receptor TrkB, the structure that BDNF binds to, was significantly reduced in mice with SCA6 disorders, leading to motor problems.
Cook mimicked the effects of exercise on a chemical level using a TrkB booster, 7,8-dihydroxyflavone (7,8-DHF), that activates the BDNF receptor and promotes the growth of brain cells. After receiving this booster, the mice who suffered from SCA6 saw similar increases in BDNF levels as they did after exercise. This indicated to Cook that 7,8-DHF may offer similar benefits in humans, allowing for a more accessible form of treatment for patients with severe movement disorders.
In the future, Watt and her team hope to show how different types of exercise can elevate BDNF levels in the brain.
“We showed that the mice that ran further showed better improvement,” Watt said in an interview with the Tribune. “We’re looking at movement disorders from many points of view—we don’t think that there’s going to be one perfect solution.”
Not only does this highlight the importance of early diagnostics for those with SCA6 and similar movement disorders, but it suggests that future research should be conducted at later disease stages.
“Some of our next steps will be to identify other treatments that mimic exercise, and other drugs that are more effective in later stages of the disease,” Cook said. “So far we have only been able to rescue ataxia in early disease stages, but to really help patients we need to understand what goes wrong later in disease and find new treatments that target those later changes.”
Cook added that with further investigation, more areas of research are opening up.
“SCA6 currently has very limited treatment options and no cure, so this is very promising research,” Cook said. “I really believe that it’s just as important to identify treatments for rare diseases as it is for the more common ones.”