Modified and stabilized GDF propeptides and uses thereof
First Claim
1. A nucleic acid molecule encoding a GDF-8 propeptide comprising a nucleic acid that hybridizes under stringent hybridization conditions, wherein hybridization is carried out at 65°
- C. in 6×
SSC, to the complement of SEQ ID NO;
6 and encodes a propeptide that is modified at the aspartate residue corresponding to aspartate 76 of SEQ ID NO;
5, wherein the encoded propeptide inhibits at least one GDF-8 biological activity.
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Abstract
Modified and stabilized propeptides of Growth Differentiation Factor proteins, such as GDF-8 and Bone Morphogenetic Protein-11, are disclosed. Also disclosed are methods for making and using the modified propeptides to prevent or treat human or animal disorders in which an increase in muscle tissue would be therapeutically beneficial. Such disorders include muscle or neuromuscular disorders (such as amyotrophic lateral sclerosis, muscular dystrophy, muscle atrophy, congestive obstructive pulmonary disease, muscle wasting syndrome, sarcopenia, or cachexia), metabolic diseases or disorders (such as such as type 2 diabetes, noninsulin-dependent diabetes mellitus, hyperglycemia, or obesity), adipose tissue disorders (such as obesity), and bone degenerative diseases (such as osteoporosis).
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Citations
20 Claims
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1. A nucleic acid molecule encoding a GDF-8 propeptide comprising a nucleic acid that hybridizes under stringent hybridization conditions, wherein hybridization is carried out at 65°
- C. in 6×
SSC, to the complement of SEQ ID NO;
6 and encodes a propeptide that is modified at the aspartate residue corresponding to aspartate 76 of SEQ ID NO;
5, wherein the encoded propeptide inhibits at least one GDF-8 biological activity. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
- C. in 6×
Specification