Customized Dietary Intervention Avoids Unintentional Weight Loss and Modulates Circulating miRNAs Footprint in Huntington's Disease

Scope: Huntington's disease (HD) is a rare progressive neurodegenerative disorder of genetic origin, with no definitive treatment. Unintentional weight loss (UWL) is a clinical feature of symptomatic HD subjects. To prevent UWL, a customized HD diet is designed and its impact on plasma miRNA HD footprint and neurological parameters is examined. Methods and results: Eleven participants are included, BMI <= 18 kg m(-2) or UWL of 5% in 6 months or 10% in a year. Diet design is based on nutritional surveys and interviews of participants and caregivers and on published literature review. Twelve-month dietary intervention, with follow-up every 3 months, induces high diet adherence, which manages to curb UWL in all participants (73% gained weight). Noticeable increases in fat mass and leptin levels are obtained. The results also show significant decrease in the expression of 19 miRNAs, which are previously reported to be upregulated in HD-patients versus healthy controls: revealing hsa-miR-338-3p, hsa-miR-128-3p, hsa-miR-23a-3p, and hsa-miR-24-3p as potential HD-biomarkers. The diminished expression of hsa-miR-100-5p reflects the general maintenance of the functional status. Cognitive status is improved in six of 11 participants, while only three present better motor-score values. Conclusion: A customized HD-diet prevents UWL and modified miRNAs HD-footprint. The normalization of miRNA values suggests its potentially use as HD-biomarkers.