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.

We claim: 
     
         1 . A method of promoting cutaneous wound healing in a subject, the method comprising the step of administering at a wound site on said subject a composition comprising an isolated glial cell derived growth factor (GDNF), or a biologically active fragment thereof, and a pharmaceutically acceptable carrier. 
     
     
         2 . The method of  claim 1 , wherein said GDNF has the amino acid sequence set forth as amino acids 78-211 of SEQ ID NO:7. 
     
     
         3 . The method of  claim 1 , wherein said GDNF is encoded by the nucleic acid sequence set forth as nucleotides 201-836 of SEQ ID NO:1 or is encoded by a nucleic acid sequence having at least 90% or at least 95% identity to the nucleic acid sequence set forth as nucleotides 201-836 of SEQ ID NO:1. 
     
     
         4 . The method of  claim 1 , wherein the biologically active fragment of GDNF has the amino acid sequence set forth as amino acids 118-211 of SEQ ID NO:7. 
     
     
         5 . The method of  claim 1 , wherein the GDNF, 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. 
     
     
         6 . The method of  claim 1 , wherein said 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. 
     
     
         7 . The method of  claim 1 , wherein said composition further comprises at least one anti-inflammatory agent. 
     
     
         8 . The method of  claim 1 , wherein said composition further comprises at least one antibiotic. 
     
     
         9 . The method of  claim 1 , wherein the composition is administered at a dose of at least about 0.1-0.5 mg/ml GDNF. 
     
     
         10 . The method of  claim 1 , wherein said administration step is repeated for a time sufficient to promote filling and re-epithelialization of a wound site. 
     
     
         11 . The method of  claim 1 , wherein said administration step is repeated for a time sufficient to reestablish a skin barrier at the wound site. 
     
     
         12 . The method of  claim 1 , wherein the administration step is repeated for a time period sufficient to promote cutaneous wound healing. 
     
     
         13 . The method of  claim 12 , wherein said administration step is repeated daily, for at least 3-5 days. 
     
     
         14 . The method of  claim 12 , wherein said administration is step is repeated twice daily, for at least 3-5 days. 
     
     
         15 . The method of  claim 1 , wherein said administration is via injection at the wound site. 
     
     
         16 . The method of  claim 1 , wherein said administration is via topical contacting at the wound site. 
     
     
         17 . The method of  claim 1 , wherein said subject has diabetes. 
     
     
         18 . A method of promoting cutaneous wound healing in a subject that has diabetes, the method comprising the step of administering at a wound site on said subject a composition comprising an isolated glial cell derived growth factor (GDNF), or a biologically active fragment thereof, and a pharmaceutically acceptable carrier. 
     
     
         19 . The method of  claim 18 , wherein said GDNF has the amino acid sequence set forth as amino acids 78-211 of SEQ ID NO:7. 
     
     
         20 . The method of  claim 18 , wherein said GDNF is encoded by the nucleic acid sequence set forth as nucleotides 201-836 of SEQ ID NO:1 or is encoded by a nucleic acid sequence having at least 90% or at least 95% identity to the nucleic acid sequence set forth as nucleotides 201-836 of SEQ ID NO:1. 
     
     
         21 . The method of  claim 18 , wherein said composition further comprises at least one anti-inflammatory agent. 
     
     
         22 . The method of  claim 18 , wherein said composition further comprises at least one antibiotic. 
     
     
         23 . the method of  claim 18 , wherein the administration step is repeated for a time period sufficient to promote cutaneous wound healing. 
     
     
         24 . A method of promoting cutaneous wound healing in a subject, the method comprising the step of administering at a wound site on said subject a composition comprising an isolated glial cell derived growth factor (GDNF), or a biologically active fragment thereof, wherein said GDNF has an amino acid sequence comprising amino acid residues 78-211 of SEQ ID NO: 7, and a pharmaceutically acceptable carrier. 
     
     
         25 . The method of  claim 24 , wherein said 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. 
     
     
         26 . The method of  claim 24 , wherein the administration step is repeated for a time period sufficient to promote cutaneous wound healing.