Objective:

Evaluate the safety, feasibility, and potential clinical and biological effects of a 12-week time-restricted eating (TRE) intervention in people with early-stage Huntington’s disease (HD).

Background:

HD is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric manifestations for which no approved disease-modifying therapies exist. TRE, a form of intermittent fasting that confines daily caloric intake to a limited eating window, has been shown to activate potentially therapeutic cellular stress-response pathways implicated in neurodegeneration. Preclinical studies suggest TRE may slow HD progression, but its safety and effects in individuals with HD remain unknown.

Design/Methods:

We conducted a single-arm, open-label interventional trial (ClinicalTrials.gov NCT06490367) in adults with early-stage HD. Participants were instructed to consume all calories within a self-selected 8-hour window each day for 12 weeks while fasting the remaining 16 hours. Primary outcomes were feasibility and safety, assessed through adherence, body composition, adverse events, and laboratory parameters. Secondary outcomes included pre- versus post-intervention changes in standard HD clinical scores and biomarkers of disease progression.

Results:

Twenty participants completed the study. Average adherence was 5.3 ± 1.0 days/week, with no significant adverse events or blood panel derangements. Body weight and fat-free mass remained stable (<1.5% change). Improvements were detected in motor symptoms, cognitive performance, and the composite UHDRS score (0.5 ± 0.7; p=0.003). We also observed significant enhancements in objective measures, including plasma NfL concentrations and peripheral blood cell mitochondrial function.

Conclusions:

A 12-week 8-hour TRE regimen appears feasible, safe, and well-tolerated in early-stage HD and may yield favorable effects on clinical and biomarker outcomes. These results establish a mechanistic and clinical foundation for further investigation of TRE as a metabolic intervention in HD and other related neurodegenerative diseases.