Gamma-sarcoglycan (SGCG) (SGCG)

Gamma-sarcoglycan is a 35 kDa type II transmembrane glycoprotein that serves as a vital component of the sarcoglycan subcomplex within the dystrophin-associated glycoprotein complex (DGC) [1, 3, 5]. Encoded by the SGCG gene, it is expressed primarily in skeletal and cardiac muscle, where it helps maintain the structural integrity of the sarcolemmal membrane by linking the intracellular cytoskeleton to the extracellular matrix [1, 9, 14]. Mutations in the SGCG gene result in the loss of the protein, leading to Limb-girdle muscular dystrophy type 2C (LGMD2C), also known as LGMDR5, a progressive muscle-wasting disease [1, 11, 16]. This condition is characterized by early-onset weakness in the pelvic and shoulder girdles, often progressing to loss of ambulation and respiratory or cardiac complications [12, 16, 18]. As a monogenic recessive disorder, Gamma-sarcoglycan is a primary target for gene replacement therapies [4, 7]. Investigational treatments such as SRP-9005 and ATA-200 utilize adeno-associated virus (AAV) vectors to deliver a functional copy of the SGCG gene to muscle cells, aiming to restore protein expression and stabilize the muscle membrane [7, 8, 10, 11]. Clinical monitoring of these therapies involves assessing protein expression via muscle biopsy and measuring serum creatine kinase levels as a biomarker of muscle damage [12, 13, 17]. Safety considerations for these treatments include potential immune responses to the viral vector or the newly expressed transgene product [7, 11].

Other names

SGCG35 kDa dystrophin-associated glycoprotein35DAGA4DAGA4DMDADMDA1LGMD2CMAMSCARMD2SCG3TYPEgamma-SGSarcoglycan gammaLGMDR5

Gene replacement therapy via adeno-associated virus (AAV) vector delivery of a functional SGCG transgene to restore protein expression and stabilize the dystrophin-associated glycoprotein complex.