Objective: Evaluate whether 12 weeks of daily time-restricted eating (TRE) appears safe and feasible in persons with early-stage Huntington’s disease (HD) and explore its effects on clinical and biomarker measures of disease progression.

Background: HD is a debilitating and eventually fatal neurodegenerative disorder for which no disease-modifying treatments exist. Novel therapeutic approaches, including lifestyle modifications, warrant further investigation [1-3]. Preclinical evidence suggests that TRE, a form of intermittent fasting, may attenuate neurodegenerative processes and slow HD progression [4]. Although it has shown therapeutic potential in animal models and non-HD populations, it has yet to be analyzed for safety, feasibility, and efficacy in persons with HD.

Method: This is a single-arm, unblinded interventional study of TRE in adults with late prodromal and early manifest HD. Participants were instructed to eat all calories within a self-selected 8-hour window every day – and fast the remaining 16 hours – for 12 weeks (NCT06490367). The primary outcome is adherence tracked via daily surveys and weekly time-stamped meal entries in a mobile device application (SnapCalorieTM). Secondary outcomes include changes in body weight and composition, routine labs, serum biomarkers of disease progression – neurofilament light protein and glial fibrillary acid protein – and standard HD clinical scales.

Results: Of the 20 planned enrollment, 13 participants have completed the study while 7 remain actively on protocol. Preliminary analysis reveals that, on average, participants successfully adhered to the diet 5.5 days/week with no reported adverse events or lab derangements. Body weight and fat-free mass remained stable (<2.5% change). Total Motor Score and Verbal Fluency Test scores have improved by 15% (p=0.0301) and 20% (p=0.0036), respectively. All measures of psychiatric symptom frequency and severity have improved by a range of 15% to 42%. Composite UHDRS score trended toward improvement of 2.5% compared to pre-treatment (p=0.0737).

Conclusion: Preliminary analysis suggests that 8-hour TRE for 12 weeks is feasible, tolerable, and safe in persons with early-stage HD. Despite limitations of this unblinded study, its findings warrant further investigation on a larger scale with a more rigorous trial design.

References: [1] Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc Natl Acad Sci U S A. 2004;101(10):3498-503 doi: 10.1073/pnas.0308679101.

[2] Trembath MK, Horton ZA, Tippett L, Hogg V, Collins VR, Churchyard A, et al. A retrospective study of the impact of lifestyle on age at onset of Huntington disease. Mov Disord. 2010;25(10):1444-50 doi: 10.1002/mds.23108.

[3] Novati A, Nguyen HP, Schulze-Hentrich J. Environmental stimulation in Huntington disease patients and animal models. Neurobiol Dis. 2022;171:105725 doi: 10.1016/j.nbd.2022.105725.

[4] Wells RG, Neilson LE, McHill AW, Hiller AL. Dietary fasting and time-restricted eating in Huntington’s disease: therapeutic potential and underlying mechanisms. Transl Neurodegener. 2024;13(1):17 doi: 10.1186/s40035-024-00406-z.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-feasibility-and-effects-of-time-restricted-eating-in-early-stage-huntingtons-disease-preliminary-analysis-of-a-clinical-pilot-trial/