Protoxin-ii variants and methods of use thereof

A method of treating Nav1.7-mediated pain in a subject, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises:

• (a) an isolated Protoxin-II variant or a fusion protein thereof, wherein the Protoxin-II variant inhibits human Nav1.7 activity with an IC50 value of about 1×10−7 M or less, about 1×10−8 M or less, about 1×10−9 M or less, about 1×10−10 M or less, about 1×10−11 M or less, or about 1×10−12 M or less, wherein the IC50 value is measured using a veratridine-induced depolarization inhibition assay using fluorescence resonance energy transfer (FRET) in the presence of 25×10−6 M 3-veratroylveracevine in HEK293 cells stably expressing human Nav1.7, wherein the Protoxin-II variant has a W7Q and/or a W30L substitution, wherein residue numbering is according to SEQ ID NO:
• 1;
• and
• (b) a pharmaceutically acceptable excipient.