Biglycan and related therapeutics and methods of use
The invention provides compositions and methods for treating, preventing, and diagnosing diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, due, e.g., 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 pharmaceutical composition comprising:
(i) a polypeptide consisting of a sequence at least 80% identical to amino acids 38-365 of SEQ ID NO: 9, wherein the polypeptide is capable of binding to alpha-sarcoglycan and gamma-sarcoglycan and does not comprise glycosaminoglycan (GAG) side chains; and
(ii) a physiologically acceptable carrier or excipient;
wherein the composition is formulated as a sterile aqueous solution suitable for systemic administration or injection.
2. The pharmaceutical composition of claim 1 , wherein the polypeptide consists of an amino acid sequence which is at least about 90% identical to amino acids 38-365 of SEQ ID NO: 9.
3. The pharmaceutical composition of claim 1 , wherein the polypeptide consists of an amino acid sequence that is at least about 95% identical to amino acids 38-365 of SEQ ID NO: 9.
4. The pharmaceutical composition of claim 1 , wherein the polypeptide is encoded by a nucleic acid which hybridizes to SEQ ID NO: 8 under stringent conditions of 6.0× sodium chloride/sodium citrate (SSC) at about 45° C. to a complementary strand of SEQ ID NO: 8.
5. The pharmaceutical composition of claim 1 , wherein the polypeptide consists of an amino acid sequence that is at least about 99% identical to amino acids 38-365 of SEQ ID NO: 9.
6. The pharmaceutical composition of claim 1 , which is formulated for injection.
7. The pharmaceutical composition of claim 6 , which is formulated for intramuscular injection.
8. The pharmaceutical composition of claim 6 , which is formulated for subcutaneous injection.
9. The pharmaceutical composition of claim 1 , which is formulated for systemic administration.
10. The pharmaceutical composition of claim 1 , which comprises a suspending, stabilizing, or dispersing agent.
11. A pharmaceutical composition comprising:
(i) a polypeptide consisting of a sequence at least 80% identical to amino acids 20-365 of SEQ ID NO: 9, wherein the polypeptide is capable of binding to alpha-sarcoglycan and gamma-sarcoglycan and does not comprise glycosaminoglycan (GAG) side chains; and
(ii) a physiologically acceptable carrier or excipient;
wherein the composition is formulated as a sterile aqueous solution suitable for systemic administration or injection.
12. The pharmaceutical composition of claim 11 , wherein the polypeptide consists of an amino acid sequence which is at least about 90% identical to amino acids 20-365 of SEQ ID NO: 9.
13. The pharmaceutical composition of claim 11 , wherein the polypeptide consists of an amino acid sequence which is at least about 95% identical to amino acids 20-365 of SEQ ID NO: 9.
14. The pharmaceutical composition of claim 11 , wherein the polypeptide consists of an amino acid sequence which is at least about 99% identical to amino acids 20-365 of SEQ ID NO: 9.
15. The pharmaceutical composition of claim 11 , which is formulated for injection.
16. The pharmaceutical composition of claim 15 , which is formulated for intramuscular injection.
17. The pharmaceutical composition of claim 15 , which is formulated for subcutaneous injection.
18. The pharmaceutical composition of claim 11 , which is formulated for systemic administration.