G.P.252 : Beta-sarcoglycanopathy: Any longer an “orphan” disease?

Abstract

Limb girdle muscular dystrophy (LGMD) constitutes a family of rare genetic disease characterized by progressive weakness of pelvic or shoulder girdle musculature due to impairment of the dystrophin-associated protein complex (DPC) components. The sarcoglycanopathies are a common cause of LGMDs, accounting for 3–18%, with a high percentage of severe cases. In particular, LGMD2E is a recessive autosomal disease caused by mutation in the gene, located on chromosome 4q12, encoding the beta-sarcoglycan, a major component of the DPC. Age of onset is between 2 years and the mid-teenage years. The clinical presentation includes progressive limb weakness (mainly of proximal muscles). Cardiac involvement occurs in 20% of the cases. LGMD2E is classified as a “neglected” disease by EU, underlying a substantial absence of dedicated scientific research; no specific treatments are known. Of interest, sarcoglycanopathies should be cured by gene therapy since the sarcoglycans genes are relatively short and with few exons, making them suitable for adenovirus-based therapy. Actually, a phase II clinical trial for gene therapy of alpha-sarcoglycanopathy is ongoing in USA. Another possible approach relies on autologous transplantation of stem cells, such as muscle progenitor cells. In 2013 the volunteer organization named Family Group of Beta-sarcoglycanopathy ONLUS (GFB ONLUS www.lgmd2e.org) was established to: a) contact the highest number of patients affected by LGMD and their families b) collect all data and information available on LGMD2E c) stimulate both basic and clinical research. Moreover, we would like to promote scientific research specific on LGMD2E, create collaborations with scientists to organize both informative and scientific meetings and, eventually, support researchers interested to study this disease. On April 19th 2013 the GFB ONLUS held its first scientific Meeting in Milan that allowed a fruitful confrontation among national and international researches. Limb girdle muscular dystrophy (LGMD) constitutes a family of rare genetic disease characterized by progressive weakness of pelvic or shoulder girdle musculature due to impairment of the dystrophin-associated protein complex (DPC) components. The sarcoglycanopathies are a common cause of LGMDs, accounting for 3–18%, with a high percentage of severe cases. In particular, LGMD2E is a recessive autosomal disease caused by mutation in the gene, located on chromosome 4q12, encoding the beta-sarcoglycan, a major component of the DPC. Age of onset is between 2 years and the mid-teenage years. The clinical presentation includes progressive limb weakness (mainly of proximal muscles). Cardiac involvement occurs in 20% of the cases. LGMD2E is classified as a “neglected” disease by EU, underlying a substantial absence of dedicated scientific research; no specific treatments are known. Of interest, sarcoglycanopathies should be cured by gene therapy since the sarcoglycans genes are relatively short and with few exons, making them suitable for adenovirus-based therapy. Actually, a phase II clinical trial for gene therapy of alpha-sarcoglycanopathy is ongoing in USA. Another possible approach relies on autologous transplantation of stem cells, such as muscle progenitor cells. In 2013 the volunteer organization named Family Group of Beta-sarcoglycanopathy ONLUS (GFB ONLUS www.lgmd2e.org) was established to: a) contact the highest number of patients affected by LGMD and their families b) collect all data and information available on LGMD2E c) stimulate both basic and clinical research. Moreover, we would like to promote scientific research specific on LGMD2E, create collaborations with scientists to organize both informative and scientific meetings and, eventually, support researchers interested to study this disease. On April 19th 2013 the GFB ONLUS held its first scientific Meeting in Milan that allowed a fruitful confrontation among national and international researches.