Huntington's disease discovery opens door to a new class of treatments

Scientists at Lawrence Berkeley National Laboratory have uncovered a potential new treatment for Huntington's disease, a fatal and inherited neurodegenerative condition. The research led by Aris Polyzos and Cynthia McMurray reveals that an increase in DNA breaks across the genome appears to be driving the neurodegeneration associated with HD.

The mutated huntingtin protein, which is the cause of Huntington's disease, leads to the death of neurons in specific brain regions as people age. Over time, the mutated gene accumulates more repeating sequences, causing the disease to onset earlier and manifest more severe symptoms.

However, the new study published in Nature Communications shows that an antioxidant treatment can suppress these DNA breaks and reverse neuronal damage in mice with Huntington's disease. This discovery was made after researchers examined energy uptake in HD neurons and found that support cells for neurons in the brain region most affected by HD switched to using fatty acids for fuel, leading to an increased generation of reactive oxygen species (ROS).

ROS are highly reactive molecules that can damage DNA, and the study found a surprising accumulation of double-stranded DNA breaks (DSBs) in the neurons of HD patients. The mutation in the huntingtin gene appears to suppress the normal DNA repair enzymes responsible for fixing these breaks.

The researchers believe that targeting these DNA breaks with an antioxidant compound could be a simpler and more effective approach than previous treatments that focused on editing the gene or stopping its expansion. The next step is to confirm if these findings apply to human cells and to conduct clinical trials.