Limb girdle muscular disease caused by HMGCR mutation and statin myopathy treatable with mevalonolactone
Abstract
Limb girdle muscular dystrophies (LGMD) are a group of genetic diseases, whose causative mutations are only partly known, with no currently available definitive treatment. Statins, a lipid-lowering drug class, act by inhibiting HMG-CoA reductase, encoded by HMGCR, and show a common side effect—myopathy. The cause of statin myopathy is mostly unknown and treatment is limited. We show that a severe progressive hereditary myopathy, greatly overlapping with statin myopathy, is caused by HMGCR mutation. We demonstrate that treatment with oral mevalonolactone, never used to treat patients before, is effective and safe both in HMGCR-myopathy in humans and statin-myopathy in mice. Thus, this work sheds light on molecular pathways of statin myopathy and LGMD, delineating effective specific treatment for both.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- February 2023
- DOI:
- Bibcode:
- 2023PNAS..12017831Y