Methods for promoting wound healing and hair growth

Abstract

The present invention generally relates to uses of glial cell line-derived growth factor (GDNF) in cutaneous wound healing and hair growth. Methods of effecting hair growth and/or wound healing which feature administration of GDNF, or a biologically active fragment thereof, to subjects, e.g., human subject, are disclosed herein. The invention relates also to formulations and kits for achieving the indicated pharmaceutical advantages.

1 . A pharmaceutical formulation comprising a dose of isolated glial cell derived growth factor (GDNF) polypeptide, or a biologically active fragment thereof, effective to promote cutaneous wound healing in a subject, in combination with at least one agent which facilitates administration of the polypeptide, or a biologically active fragment thereof. 
     
     
         2 . The pharmaceutical formulation of  claim 1 , wherein the polypeptide comprises the amino acid sequence of amino acids 78-211 of SEQ ID NO:7 or the amino acid sequence of amino acids 118-211 of SEQ ID NO:7. 
     
     
         3 . The pharmaceutical formulation of  claim 1 , wherein the polypeptide is encoded by the nucleic acid sequence comprising nucleotides 201-836 of SEQ ID NO:1 or is encoded by a nucleic acid sequence having at least 90% or 95% identity to the nucleic acid sequence comprising nucleotides 201-836 of SEQ ID NO:1. 
     
     
         4 . The pharmaceutical formulation of  claim 1 , wherein the polypeptide, or biologically active fragment thereof is glycosylated at the glycosylation site occurring at amino acid residues 126-128 of SEQ ID NO:7 or at the glycosylation site occurring at amino acid residues 162-164 of SEQ ID NO:7. 
     
     
         5 . The pharmaceutical formulation of  claim 1 , wherein the wound site is selected from the group consisting of an incision, a laceration, an abrasion, a puncture wound, a penetration wound, a surgical wound, an ulceration, a burn, a contusion, a hematoma, and crush injury. 
     
     
         6 . The pharmaceutical formulation of  claim 1 , wherein the formulation further comprises at least one anti-inflammatory agent or at least one antibiotic. 
     
     
         7 . The pharmaceutical formulation of  claim 1 , wherein the formulation is administered to the subject at a dose of at least about 0.1-0.5 mg/ml GDNF. 
     
     
         8 . The pharmaceutical formulation of  claim 1 , wherein the formulation is administered to the subject and administration is repeated for a time sufficient to promote filling and re-epithelialization of a wound site; or administration is repeated for a time sufficient to reestablish a skin barrier at the wound site. 
     
     
         9 . The pharmaceutical formulation of  claim 1 , wherein the formulation is administered to the subject and administration is repeated for a time period sufficient to promote cutaneous wound healing. 
     
     
         10 . The pharmaceutical formulation of  claim 9 , wherein administration is repeated daily, for at least 3-5 days; or repeated twice daily, for at least 3-5 days. 
     
     
         11 . The pharmaceutical formulation of  claim 1 , wherein the formulation is administered to the subject via injection at the wound site or via topical contacting at the wound site. 
     
     
         12 . The pharmaceutical formulation of  claim 1 , wherein the subject has diabetes. 
     
     
         13 . A pharmaceutical formulation comprising a dose of isolated glial cell derived growth factor (GDNF) polypeptide, or a biologically active fragment thereof, effective to promote hair growth on a subject, in combination with at least one agent which facilitates administration of the polypeptide, or a biologically active fragment thereof. 
     
     
         14 . The pharmaceutical formulation of  claim 13 , wherein the polypeptide comprises the amino acid sequence of amino acids 78-211 of SEQ ID NO:7 or the amino acid sequence of amino acids 118-211 of SEQ ID NO:7. 
     
     
         15 . The pharmaceutical formulation of  claim 13 , wherein the dose is a dose sufficient to promote a 25% increase in hair follicle number or a 25% decrease in hair loss over a period of 3-4 months. 
     
     
         16 . The pharmaceutical formulation of  claim 13 , wherein the formulation is administered to the subject via topical contacting at the site of desired hair growth. 
     
     
         17 . The pharmaceutical formulation of  claim 13 , wherein the GDNF is glycosylated at the glycosylation site occurring at amino acid residues 126-128 of SEQ ID NO:7 or at the glycosylation site occurring at amino acid residues 162-164 of SEQ ID NO:7. 
     
     
         18 . The pharmaceutical formulation of  claim 13 , wherein the dose consists of no more than about 10 mg/ml GDNF. 
     
     
         19 . The pharmaceutical formulation of  claim 13 , wherein the formulation is administered to the subject and the administration is repeated for a time period sufficient to promote hair growth. 
     
     
         20 . The pharmaceutical formulation of  claim 19 , wherein the repeating step is performed five times.