Methods and compositions for treatment of myotubular myopathy using chimeric polypeptides comprising myotubularin 1(MTM1) polypeptides

摘要

The present invention provides chimeric polypeptides comprising myotubularin 1 (MTMI) polypeptides and an internalizing moiety, wherein, the moiety can be an antibody, and is preferably monoclonal antibody 3E10, a functional variant or a fragment thereof. One aspect of the present invention provides compositions comprising these chimeric polypeptides together with a pharmaceutically acceptable carrier, and optionally, a further therapeutic agent. Another aspect of the present invention provides methods of treating Myotubular Myopathy comprising administering the polypeptides or compositions comprising the polypeptides to a subject in need.

主权项

1. A chimeric polypeptide comprising: (i) a myotubularin (MTM1) polypeptide, or a bioactive fragment thereof; wherein the MTM1 polypeptide comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1, and (ii) an internalizing moiety,
wherein the chimeric polypeptide has phosphoinositide phosphatase activity; wherein said internalizing moiety is an antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof is a monoclonal antibody 3E10, or a variant thereof that retains the cell penetrating activity of 3E10, or an antigen-binding fragment of any of the foregoing.