Biglycan mutants and related therapeutics and methods of use
The present disclosure provides compositions and methods for treating diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, for example, due to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of diseases include muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders.
1. A method for treating a muscular dystrophy in a subject, comprising administering to the subject an effective amount of a biglycan-related polypeptide comprising an amino acid sequence corresponding to amino acids 38-365 of SEQ ID NO: 11, which biglycan-related polypeptide comprises less than 1% total carbohydrate by weight.
2. The method of claim 1 , wherein the muscular dystrophy is selected from Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Congenital Muscular Dystrophy, Limb-girdle Muscular Dystrophy, and myotonic dystrophy.
3. A method for treating amyotrophic lateral sclerosis in a subject, comprising administering to the subject an effective amount of a biglycan-related polypeptide comprising an amino acid sequence corresponding to amino acids 38-365 of SEQ ID NO: 11, which biglycan-related polypeptide comprises less than 1% total carbohydrate by weight.
4. A method for treating Bethlem's myopathy, Ullrich Congenital Muscular Dystrophy, or Sorsby's fundus dystrophy, comprising administering to the subject an effective amount of a biglycan-related polypeptide comprising an amino acid sequence corresponding to amino acids 38-365 of SEQ ID NO: 11, which biglycan-related polypeptide comprises less than 1% total carbohydrate by weight.