Current and Future Therapeutic Strategies for Limb Girdle Muscular Dystrophy Type R1: Clinical and Experimental Approaches

Abstract

Limb girdle muscular dystrophy type R1 disease is a progressive disease that is caused by mutations in the CAPN3 gene and involves the extremity muscles of the hip and shoulder girdle. The CAPN3 protein has proteolytic and non-proteolytic properties. The functions of the CAPN3 protein that have been determined so far can be listed as remodeling and combining contractile proteins in the sarcomere with the substrates with which it interacts, controlling the Ca2+ flow in and out through the sarcoplasmic reticulum, and regulation of membrane repair and muscle regeneration. Even though there are several gene therapies, cellular therapies, and drug therapies, such as glucocorticoid treatment, AAV- mediated therapy, CRISPR-Cas9, induced pluripotent stem cells, MYO-029, and AMBMP, which are either in preclinical or clinical phases, or have been completed, there is no final cure. Inhibitors and small molecules (tauroursodeoxycholic acid, salubrinal, rapamycin, CDN1163, dwarf open reading frame) targeting ER stress factors that are thought to be effective in muscle loss can be considered potential therapy strategies. At present, little can be done to treat the progressive muscle wasting, loss of function, and premature mortality of patients with LGMDR1, and there is a pressing need for more research to develop potential therapies.

Identification and functional characterization of a novel heterozygous splice‑site mutation in the calpain 3 gene causes rare autosomal dominant limb‑girdle muscular dystrophy

“…At present, several gene therapy-based strategies have been used to treat patients with LGMDD4 that harbor a CAPN3 mutation. Moreover, cellular therapies, drug therapies (glucocorticoid treatment) or gene therapies (AAV-mediated therapy and CRISPR-Cas9 gene editing) have been performed either in preclinical or clinical phases; however, there is no cure ( 63 ). Endoplasmic reticulum stress factor-targeting inhibitors and small molecules (tauroursodeoxycholic acid, salubrinal and rapamycin) have also been considered as potential therapeutic strategies ( 11 ).…”

Management of a 25-Year-Old Female Patient With Limb-Girdle Muscular Dystrophy With Physiotherapy: A Case Report

“…There is currently no effective pharmacologic therapy for LGMD, even though numerous therapeutic regimens have been proposed [ 18 ]. Patients must, therefore, rely on symptomatic care, in which ongoing physical therapy is essential.…”