January 18, 2026

@michaelokun

Check out this comprehensive 2025 Update on Huntington’s disease. Spoiler alert: In 2025 we learned something crucial about how somatic mutations in HD are crucially related to disease manifestation. Huntington’s disease is a genetic brain disorder caused by a repeating DNA code (CAG) that gradually disrupts movement, thinking and behavior. Donaldson and colleagues describe in a new paper in Nature Reviews Neurology how Huntington’s disease biology is being reframed and where new therapeutic opportunities are emerging. Key points: -Somatic expansion of the CAG repeat in brain cells is now viewed as a major driver of disease onset and progression. - DNA repair pathways strongly influence when symptoms begin and how fast the disease advances. - Targeting repeat expansion may complement huntingtin lowering approaches for longer lasting benefit. My take: This review marks a real shift in how we think about Huntington’s disease. It is not only about a toxic protein but also about unstable DNA that keeps changing over time. That insight opens doors to earlier and potentially broader interventions across repeat expansion diseases. 5 points that resonated w/ me: 1- Disease progression appears to be shaped at the DNA level, not just the protein level. 2- Small changes in DNA repair can meaningfully alter when symptoms begin for folks. 3- Slowing somatic repeat expansion could delay disease even before the symptoms emerge. 4- Combining DNA targeted strategies w/ huntingtin lowering may be more effective than either approach alone. 5- Biomarkers that track repeat expansion will be essential to move these therapies forward for health care providers and for persons w/ disease. https://www.nature.com/articles/s41582-025-01159-7 #michaelokun #fixelinstitute #huntingtonsdiseaseawareness