Multiprotease Therapeutics for Chronic Pain

摘要

The invention includes Clostridial neurotoxin derivatives containing at least two light chain endopeptidase domains, and nucleic acids encoding such Clostridial neurotoxin derivatives. In preferred embodiments, the invention includes methods and compositions for the treatment of inflammatory disorders (such as arthritis); chronic pain, such as neuropathic pain and inflammatory pain through the use of such Clostridial neurotoxin derivatives, including those derived from an intact BoNT/A having an LC/E-derived endopeptidase joined to the LC/A endopeptidase.

主权项

1) A nucleic acid encoding a polypeptide comprising a Clostridial neurotoxin derivative, said nucleic acid comprising a single open reading frame encoding, in sequence from carboxyterminus to amino terminus: a binding domain comprising an HCN subdomain and an HCC subdomain, a translocation domain, a first endopeptidase domain, and a second endopeptidase domain different from said first endopeptidase domain, wherein each of said first endopeptidase domain and said second endopeptidase domain has a selective proteolytic activity against, and said first and second endopeptidase domains recognize different cleavage sites in, a SNARE protein.