title: Single muscle fiber contractile properties in adults with muscular dystrophy treated with MYO-029.
abstract: Myostatin inhibitors are being investigated as treatments for myopathies. We assessed single muscle fiber contractile properties before and after 6 months of study drug in 6 patients with facioscapulohumeral, Becker, and limb-girdle muscular dystrophy. Five of the patients received MYO-029, a myostatin inhibitor, and 1 received placebo. The chemically skinned single muscle fiber preparation was used to measure single fiber force, specific force, maximum unloaded shortening velocity, power, and specific power in type I and IIa fibers from each subject. In 4 of 5 patients who received MYO-029, improvement was seen in single muscle fiber contractile properties; thus, there may be a beneficial effect of myostatin inhibition on muscle physiology at the cellular level. No improvement was seen in the patient who received placebo. This finding may be clinically relevant in spite of the fact that quantitative muscle strength measurements in our patients did not improve. Further studies of myostatin inhibition as a treatment for muscular dystrophy are warranted, and single muscle fiber contractile studies are a useful assay for muscle function at the cellular level.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. lkrivickas@partners.org
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Krivickas
authors.forename: Ronan
authors.initials: R
authors.lastname: Walsh
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Amato
mesh_terms: D000328:Adult; D000906:Antibodies / Q000008:administration & dosage* / Q000009:adverse effects; D001681:Biological Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010919:Placebos; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; C525911:MSTN protein, human; D055435:Myostatin; D010919:Placebos; C506829:Stamulumab