The Limb–Girdle Muscular Dystrophies: Is Treatment on the Horizon?

Abstract

There has been an ever-expanding list of the Limb-Girdle Muscular Dystrophies (LGMD). There are currently 8 subtypes of autosomal dominant (AD) and 26 subtypes of autosomal recessive (AR) LGMD. Despite continued research efforts to conquer this group of genetic neuromuscular disease, patients continue to be treated symptomatically with the aim of prevention or addressing complications. Mouse models have been helpful in clarifying disease pathogenesis as well as strategizing pathways for treatment. Discoveries in translational research as well as molecular therapeutic approaches have kept clinicians optimistic that more promising clinical trials will lead the way to finding the cure for these devastating disorders. It is well known that the challenge for these rare diseases is the ability to assemble adequate numbers of patients for a clinically meaningful trial, but current efforts in developing patient registries have been encouraging. Natural history studies will be essential in establishing and interpreting the appropriate outcome measures for clinical trials. Nevertheless, animal studies continue to be key in providing proof of concept that will be necessary in moving research along. This review will briefly discuss each type of LGMD, highlighting their distinguishing features, then focus on research efforts that have been published in the literature for the past few years, many of which are still in the preclinical trial stage.

Prevalence, pathological mechanisms, and genetic basis of limb‐girdle muscular dystrophies: A review

“…LGMD2G (telethoninopathy), LGMD2I, 2K, 2M, 2N, 2O, 2P, 2T, 2U (the dystroglycanopathies), LGMD2J (titinopathy), LGMD2L, and other LGMD subtypes that are presented in Tables 1 and 2. Based on the inheritance pattern, LGMDs are divided into AR and autosomal dominant with several forms in each group and there are currently eight (10%) forms of autosomal dominant (AD) and 26 (90%) forms of AR for LGMD (Chu & Moran, 2018). Autosomal recessive forms include sarcoglycanopathies, calpainopathy, dysferlinopathy, and other forms that are presented in Table 1. LGMDs with onset before age 10 years are usually sarcoglycanopathies, dystroglycanopathies, and some calpainopathies (Magri et al, 2017).…”

CRISPR-cas gene-editing as plausible treatment of neuromuscular and nucleotide-repeat-expansion diseases: A systematic review

“…Dysfunctional or absent α-sarcoglycan brings instability in the costameres, causing the more severe disease phenotype that is LGMD2D. [98]…”

Диагностика Поясной Труднокурабельной Миопатии С Использованием Метода МРТ (Научный Обзор И Личное Наблюдение)

“…Станом на 2018 рік відомо про існування 8 підтипів КПМД типу 1 і 26 підтипів КПМД типу 2 [5] залежно від дефектного білка саркогліканового та дистрогліканового комплексів [6] (рис. 1) [7].…”