Long before Huntington's disease: what matters most?

摘要

Huntington's disease is an inherited, autosomal dominant, neurodegenerative disease. It manifests in adults through motor, cognitive, and psychiatric symptoms, typically leading to death in approximately 20 years from symptom onset. Because of its full penetrance, carriers of the mutated huntingtin gene with more than 40 CAG repeats will inevitably develop the disease. This predictability might provide an opportunity for early intervention with the emergence of disease-modifying therapies to lower mutant huntingtin protein concentrations. In The Lancet Neurology, Rachael Scahill and colleagues report results from the Huntington's disease Young Adult Study (HD-YAS), in which they aimed to determine the best biomarkers for use in studies of disease-modifying therapies in young adult gene carriers (premanifest Huntington's disease [preHD]) far from predicted clinical symptom onset. Predicted age at clinical onset (defined by the appearance of motor symptoms) was estimated through the disease burden score combining age and number of CAG repeats. The investigators enrolled 64 participants with preHD (mean age 29.0 years [SD 5.6]) who were 23.6 years (SD 5.8) from predicted clinical onset, and 67 healthy controls matched for age, education, and sex. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. Participants underwent neuropsychiatric and cognitive assessments, imaging (for those without contraindications), and assessment of biofluid markers from samples of blood and CSF collected from 83% of participants.