Sarcoglycanopathies are due to the loss of function of the sarcoglycan complex.

Different types of mutations are responsible for sarcoglycan complex disruption.

Gene replacement strategy is currently in the early phase of a clinical trial.

Compounds correcting the mutated sarcoglycan are at an advanced preclinical stage.

Sarcoglycanopathies are rare autosomal recessive diseases belonging to the family of limb-girdle muscular dystrophies. They are caused by mutations in the genes coding for α-, β-, γ-, and δ-sarcoglycan. The mutations impair the assembly of a key structural complex, which normally protects the sarcolemma of striated muscle from contraction-derived stress. Although heterogeneous, sarcoglycanopathies are characterized by progressive muscle degeneration, increased serum creatine kinase levels, loss of ambulation often during adolescence, and variable cardio-respiratory impairment. Genetic defects can impair sarcoglycan synthesis or produce a protein that is defective in folding. There is currently no effective treatment available; however, both gene replacement strategy and small molecule-based approaches show great promise and have entered or are starting to enter clinical trials.

Therapeutic approaches for sarcoglycanopathies based on gene replacement and small molecules inducing either protein recovery or acting on secondary causes of the disease. Combined approaches are also envisaged.Download : Download high-res image (150KB)Download : Download full-size image

Therapeutic approaches for sarcoglycanopathies based on gene replacement and small molecules inducing protein recovery or acting on secondary causes of the disease. Created with Biorender.com.

© 2024 The Author(s). Published by Elsevier Ltd.