An investigation by the Research Groups of the Neuromuscular Diseases Unit (Alonso-Pérez and Díaz-Manera) and of Genetic Diseases (Gallano and González-Quereda), of the Sant Pau Research Institute- IIB Sant Pau, has recently been published in the Brain journal. The results of the study, in which 33 hospitals from 13 European countries participated and which collected clinical and genetic data from 439 muscular dystrophy patients, will help to design new clinical trials in a more rational way, while indicating that those therapies that induce protein expression above 30% can produce a significant change in the natural history of the disease.
The main finding of this study is that a childhood onset, before the age of 10 years, as well as the expression of residual protein less than 30% is associated with a loss of ambulation before the age of 18 years. In contrast, a late onset of the disease and a residual expression greater than 30% is associated with a more benign phenotype, a slower evolution of the disease and a longer time of conserved ambulation. These data will help to design clinical trials in a more rational way and indicate that those therapies that induce protein expression above 30% can produce a significant change in the natural history of the disease.
Sarcoglycan-deficiency muscular dystrophy is a rare disease caused by mutations in four genes encoding alpha, beta, delta, or gamma-sarcoglycan proteins. These proteins are located in the membrane of muscle fibers where they are part of a complex of proteins responsible for maintaining the integrity of the fibers with each muscle contraction. Most patients develop rapidly progressing muscle weakness during childhood, which can lead to loss of ambulation during adolescence. However, there are cases described with a more benign phenotype presenting onset in adulthood. Genotype-phenotype correlations are still unknown.
New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.
Alonso-Pérez J, González-Quereda L, Bello L, Guglieri M, Straub V, Gallano P, Semplicini C, Pegoraro E, Zangaro V, Nascimento A, Ortez C, Comi GP, Dam LT, De Visser M, van der Kooi AJ, Garrido C, Santos M, Schara U, Gangfuß A, Løkken N, Storgaard JH, Vissing J, Schoser B, Dekomien G, Udd B, Palmio J, D’Amico A, Politano L, Nigro V, Bruno C, Panicucci C, Sarkozy A, Abdel-Mannan O, Alonso-Jimenez A, Claeys KG, Gomez-Andrés D, Munell F, Costa-Comellas L, Haberlová J, Rohlenová M, Elke V, De Bleecker JL, Dominguez-González C, Tasca G, Weiss C, Deconinck N, Fernández-Torrón R, López de Munain A, Camacho-Salas A, Melegh B, Hadzsiev K, Leonardis L, Koritnik B, Garibaldi M, de Leon-Hernández JC, Malfatti E, Fraga-Bau A, Richard I, Illa I, Díaz-Manera J.
Brain. 2020 Sep 1;143(9):2696-2708. doi: 10.1093/brain/awaa228.