Correction of Biochemical Abnormalities and Improved Muscle Function in a Phase I/II Clinical Trial of Clenbuterol in Pompe Disease

Molecular Therapy : the Journal of the American Society of Gene Therapy
Dwight D KoeberlPriya S Kishnani

Abstract

This 52-week, phase I/II double-blind, randomized, placebo-controlled study investigated the novel use of clenbuterol in late-onset Pompe disease (LOPD) stably treated with ERT. Eleven of thirteen participants completed the study. No serious adverse events were related to clenbuterol, and transient minor adverse events included mild elevations of creatine kinase, muscle spasms, and tremors. At week 52, the 6-min walk test distance increased by a mean of 16 m (p = 0.08), or a mean of 3% of predicted performance (p = 0.03), and the maximum inspiratory pressure increased 8% (p = 0.003) for the clenbuterol group. The quick motor function test score improved by a mean of seven points (p = 0.007); and the gait, stairs, gower, chair test improved by a mean of two points (p = 0.004). Clenbuterol decreased glycogen content in the vastus lateralis by 50% at week 52. Transcriptome analysis revealed more normal muscle gene expression for 38 of 44 genes related to Pompe disease following clenbuterol. The placebo group demonstrated no significant changes over the course of the study. This study provides initial evidence for safety and efficacy of adjunctive clenbuterol in patients with LOPD (NCT01942590).

Associated Clinical Trials

Citations

Jul 13, 2019·Human Gene Therapy·Pasqualina Colella, Federico Mingozzi
Jun 23, 2019·Human Molecular Genetics·Priya S KishnaniDwight D Koeberl
Sep 24, 2020·Biomolecules·Naresh K Meena, Nina Raben
Jan 14, 2021·Nature Communications·Roberta SartoriMarco Sandri
May 7, 2021·Communications Biology·Jason WangNenad Bursac
Jan 8, 2020·Molecular Therapy. Methods & Clinical Development·Sang-Oh HanDwight D Koeberl
Oct 23, 2021·The Journal of Physiology·Morten Hostrup, Johan Onslev

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