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Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington disease

By Fanny Mochel, Sandrine Duteil, Cecilia Marelli, Céline Jauffret, Agnès Barles, Janette Holm, Lawrence Sweetman, Jean-François Benoist, Daniel Rabier, Pierre G Carlier and Alexandra Durr


International audienceBackground: We previously identified a systemic metabolic defect associated with early weight loss in patients with Huntington disease (HD) suggesting a lack of substrates for the Krebs cycle. Dietary anaplerotic therapy with triheptanoin is used in clinical trials to promote energy production in patients with peripheral and brain Krebs cycle deficit, as its metabolites - C5 ketone bodies - cross the blood brain barrier. Methods: We conducted a short-term clinical trial in six HD patients (UHDRS= 33 ±13, 15-49) to monitor the tolerability of triheptanoin. We also assessed peripheral markers of short-term efficacy that were shown to be altered in early stages of HD, i.e. low serum IGF1 and 31P-NMR spectroscopy (NMRS) in muscle. Results: At baseline, 31P-NMRS displayed two patients with end-exercise muscle acidosis despite a low work output. On day 2, the introduction of triheptanoin was well tolerated in all patients, and in particular, there was no evidence of mitochondrial overload from triheptanoin-derived metabolites. After 4 days of triheptanoin-enriched diet, muscle pH regulation was normalized in the two patients with pre-treatment metabolic abnormalities. A significant increase of serum IGF1 was also observed in all patients (205 ng/ml ±60 versus 246 ng/ml ±68, p=0.010). Conclusion: This study provides a rationale for extending our anaplerotic approach with triheptanoin in HD

Topics: Huntington disease, clinical trial, Krebs cycle
Publisher: Nature Publishing Group
Year: 2010
DOI identifier: 10.1038/ejhg.2010.72
OAI identifier: oai:HAL:hal-00540038v1
Provided by: Hal-Diderot

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