Fibroblast growth factor-9 promotes hair follicle regeneration after wounding

Abstract

The present invention provides methods for treating hair loss, treating, inhibiting, or suppressing a degenerative skin disorder, treating androgenetic alopecia (AGA), generating new hair follicles (HF), and increasing the size of existing HF. The methods comprise epidermal disruption or administration of wnt, and administration of a fibroblast growth factor-9 polypeptide or another compound that upregulates sonic hedgehog gene signaling.

What is claimed is: 
     
         1 . A method of treating hair loss in a subject comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a fibroblast growth factor-9 polypeptide to said subject. 
     
     
         2 . The method of  claim 1 , wherein said hair loss is due to androgenetic alopecia (AGA). 
     
     
         3 . The method of  claim 2 , wherein said AGA is male pattern baldness. 
     
     
         4 . The method of  claim 2 , wherein said AGA is female pattern baldness. 
     
     
         5 . The method of  claim 1 , wherein said hair loss is the result of a skin injury. 
     
     
         6 . The method of  claim 1 , wherein said hair loss is in the scalp or eyebrow of said subject. 
     
     
         7 . The method of  claim 1 , wherein said hair loss is in scarred skin tissue of said subject. 
     
     
         8 . The method of  claim 1 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         9 . The method of  claim 1 , wherein said step of disrupting is performed by exposing the region of said hair loss to a mechanical or chemical stimulus. 
     
     
         10 . The method of  claim 1 , wherein said step of disrupting is performed by exposing the region of said hair loss to radiation. 
     
     
         11 . The method of  claim 1 , wherein said administering step is via topical administration. 
     
     
         12 . The method of  claim 1 , wherein said administering step is via subepidermal administration. 
     
     
         13 . A method for generating a hair follicle in the dermis of a subject with hair loss comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a fibroblast growth factor-9 polypeptide to said subject. 
     
     
         14 . The method of  claim 13 , wherein said subject has a reduced number of hair follicles as a result of androgenetic alopecia (AGA). 
     
     
         15 . The method of  claim 14 , wherein said AGA is male pattern baldness. 
     
     
         16 . The method of  claim 14 , wherein said AGA is female pattern baldness. 
     
     
         17 . The method of  claim 13 , wherein said subject has a reduced number of hair follicles as a result of a skin injury. 
     
     
         18 . The method of  claim 13 , wherein said subject has a reduced number of hair follicles in the scalp or eyebrow. 
     
     
         19 . The method of  claim 13 , wherein said subject has a reduced number of hair follicles in scarred skin tissue. 
     
     
         20 . The method of  claim 13 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         21 . The method of  claim 13 , wherein said step of disrupting is performed by exposing said region of hair loss to a mechanical or chemical stimulus. 
     
     
         22 . The method of  claim 13 , wherein said step of disrupting is performed by exposing the region of said hair loss to radiation. 
     
     
         23 . The method of  claim 13 , wherein said administering step is via topical administration. 
     
     
         24 . The method of  claim 13 , wherein said administering step is via subepidermal administration. 
     
     
         25 . A method for increasing the size of a hair follicle in the dermis of a subject with hair loss comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a fibroblast growth factor-9 polypeptide to said subject. 
     
     
         26 . The method of  claim 25 , wherein said subject has reduced hair follicle size as a result of androgenetic alopecia (AGA). 
     
     
         27 . The method of  claim 26 , wherein said AGA is male pattern baldness. 
     
     
         28 . The method of  claim 26 , wherein said AGA is female pattern baldness. 
     
     
         29 . The method of  claim 25 , wherein said subject has reduced hair follicle size as a result of a skin injury. 
     
     
         30 . The method of  claim 25 , wherein said subject has reduced hair follicle size in the scalp or eyebrow. 
     
     
         31 . The method of  claim 25 , wherein said subject has reduced hair follicle size in scarred skin tissue. 
     
     
         32 . The method of  claim 25 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         33 . The method of  claim 25  wherein said step of disrupting is performed by exposing said region of hair loss to a mechanical or chemical stimulus. 
     
     
         34 . The method of  claim 25 , wherein said step of disrupting is performed by exposing the region of said hair loss to radiation. 
     
     
         35 . The method of  claim 25 , wherein said administering step is via topical administration. 
     
     
         36 . The method of  claim 25 , wherein said administering step is via subepidermal administration. 
     
     
         37 . A method for increasing hair follicle formation in the skin of a subject with hair loss comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a fibroblast growth factor-9 polypeptide to said subject. 
     
     
         38 . The method of  claim 37 , wherein said subject has decreased hair follicle numbers as a result of androgenetic alopecia (AGA). 
     
     
         39 . The method of  claim 37 , wherein said subject has decreased hair follicle numbers as a result of a skin injury. 
     
     
         40 . The method of  claim 37 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         41 . The method of  claim 37 , wherein said step of disrupting is performed by exposing a region of said dermis of said subject comprising low hair follicle numbers to a mechanical or chemical stimulus or to radiation. 
     
     
         42 . The method of  claim 37 , wherein said administering step is via topical administration. 
     
     
         43 . The method of  claim 37 , wherein said administering step is via subepidermal administration. 
     
     
         44 . A method for treating, inhibiting, or suppressing a degenerative skin disorder comprising the steps of (a) disrupting the epidermis in the region of said degenerative skin disorder in said subject and (b) administering a composition comprising a fibroblast growth factor-9 polypeptide to said subject. 
     
     
         45 . The method of  claim 44 , wherein said degenerative skin disorder is granuloma annulare. 
     
     
         46 . The method of  claim 44 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         47 . The method of  claim 44 , wherein said step of disrupting is performed by exposing said region of said degenerative skin disorder to a mechanical or chemical stimulus or to radiation. 
     
     
         48 . The method of  claim 44 , wherein said administering step is via topical administration. 
     
     
         49 . The method of  claim 44 , wherein said administering step is via subepidermal administration. 
     
     
         50 . A method for treating an androgenetic alopecia (AGA) in a scalp of a subject comprising the steps of (a) disrupting the epidermis in the region of said AGA in said subject and (b) administering a composition comprising a fibroblast growth factor-9 polypeptide to said subject. 
     
     
         51 . The method of  claim 50 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         52 . The method of  claim 50 , wherein said step of disrupting is performed by exposing the region of said AGA to a mechanical or chemical stimulus or to radiation. 
     
     
         53 . The method of  claim 50 , wherein said administering step is via topical administration. 
     
     
         54 . The method of  claim 50 , wherein said administering step is via subepidermal administration. 
     
     
         55 . A method of treating hair loss in a subject comprising the step administering a composition comprising a fibroblast growth factor-9 polypeptide and a wnt polypeptide to said subject. 
     
     
         56 . The method of  claim 55 , wherein said wnt polypeptide is a wnt7 polypeptide. 
     
     
         57 . The method of  claim 55 , wherein said hair loss is due to androgenetic alopecia (AGA). 
     
     
         58 . The method of  claim 57 , wherein said AGA is male pattern baldness. 
     
     
         59 . The method of  claim 57 , wherein said AGA is female pattern baldness. 
     
     
         60 . The method of  claim 55 , wherein said hair loss is the result of a skin injury. 
     
     
         61 . The method of  claim 55 , wherein said hair loss is in the scalp or eyebrow of said subject. 
     
     
         62 . The method of  claim 55 , wherein said hair loss is in scarred skin tissue of said subject. 
     
     
         63 . The method of  claim 55 , wherein said administering step is via topical administration. 
     
     
         64 . The method of  claim 55 , wherein said administering step is via subepidermal administration. 
     
     
         65 . A method for generating a hair follicle in the dermis of a subject comprising the step of administering a composition comprising a fibroblast growth factor-9 polypeptide and a wnt polypeptide to said subject. 
     
     
         66 . The method of  claim 65 , wherein said wnt polypeptide is a wnt7 polypeptide. 
     
     
         67 . The method of  claim 65 , wherein said subject has a reduced number of hair follicles as a result of androgenetic alopecia (AGA). 
     
     
         68 . The method of  claim 67 , wherein said AGA is male pattern baldness. 
     
     
         69 . The method of  claim 67 , wherein said AGA is female pattern baldness. 
     
     
         70 . The method of  claim 65 , wherein said subject has a reduced number of hair follicles as a result of a skin injury. 
     
     
         71 . The method of  claim 65 , wherein said subject has a reduced number of hair follicles in the scalp or eyebrow. 
     
     
         72 . The method of  claim 65 , wherein said subject has a reduced number of hair follicles in scarred skin tissue. 
     
     
         73 . The method of  claim 65 , wherein said administering step is via topical administration. 
     
     
         74 . The method of  claim 65 , wherein said administering step is via subepidermal administration. 
     
     
         75 . A method for increasing the size of a hair follicle in the dermis of a subject comprising the step of administering a composition comprising a fibroblast growth factor-9 polypeptide and a wnt polypeptide to said subject. 
     
     
         76 . The method of  claim 75 , wherein said wnt polypeptide is a wnt7 polypeptide. 
     
     
         77 . The method of  claim 75 , wherein said subject has reduced hair follicle size as a result of androgenetic alopecia (AGA). 
     
     
         78 . The method of  claim 77 , wherein said AGA is male pattern baldness. 
     
     
         79 . The method of  claim 77 , wherein said AGA is female pattern baldness. 
     
     
         80 . The method of  claim 75 , wherein said subject has reduced hair follicle size as a result of a skin injury. 
     
     
         81 . The method of  claim 75 , wherein said subject has reduced hair follicle size in the scalp or eyebrow. 
     
     
         82 . The method of  claim 75 , wherein said subject has reduced hair follicle size in scarred skin tissue. 
     
     
         83 . The method of  claim 75 , wherein said administering step is via topical administration. 
     
     
         84 . The method of  claim 75 , wherein said administering step is via subepidermal administration. 
     
     
         85 . A method for increasing hair follicle formation in the skin of a subject comprising the step of administering a composition comprising a fibroblast growth factor-9 polypeptide and a wnt polypeptide to said subject. 
     
     
         86 . The method of  claim 85 , wherein said wnt polypeptide is a wnt7 polypeptide. 
     
     
         87 . The method of  claim 85 , wherein said subject has decreased hair follicle numbers as a result of androgenetic alopecia (AGA). 
     
     
         88 . The method of  claim 85 , wherein said subject has decreased hair follicle numbers as a result of a skin injury. 
     
     
         89 . The method of  claim 85 , wherein said administering step is via topical administration. 
     
     
         90 . The method of  claim 85 , wherein said administering step is via subepidermal administration. 
     
     
         91 . A method for treating, inhibiting, or suppressing a degenerative skin disorder comprising the step of administering a composition comprising a fibroblast growth factor-9 polypeptide and a wnt polypeptide to said subject. 
     
     
         92 . The method of  claim 91 , wherein said degenerative skin disorder is granuloma annulare. 
     
     
         93 . The method of  claim 91 , wherein said wnt polypeptide is a wnt7 polypeptide. 
     
     
         94 . The method of  claim 91 , wherein said administering step is via topical administration. 
     
     
         95 . The method of  claim 91 , wherein said administering step is via subepidermal administration. 
     
     
         96 . A method for treating an androgenetic alopecia (AGA) in a scalp of a subject comprising the step of administering a composition comprising a fibroblast growth factor-9 polypeptide and a wnt polypeptide to said subject. 
     
     
         97 . The method of  claim 96 , wherein said wnt polypeptide is a wnt7 polypeptide. 
     
     
         98 . The method of  claim 96 , wherein said administering step is via topical administration. 
     
     
         99 . The method of  claim 96 , wherein said administering step is via subepidermal administration. 
     
     
         100 . A method of treating hair loss in a subject comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a compound or factor that upregulates sonic hedgehog (SHH) to said subject. 
     
     
         101 . The method of  claim 100 , wherein said factor that upregulates SHH is a fibroblast growth factor-9 polypeptide. 
     
     
         102 . The method of  claim 100 , wherein said hair loss is due to androgenetic alopecia (AGA). 
     
     
         103 . The method of  claim 102 , wherein said AGA is male pattern baldness. 
     
     
         104 . The method of  claim 102 , wherein said AGA is female pattern baldness. 
     
     
         105 . The method of  claim 100 , wherein said hair loss is the result of a skin injury. 
     
     
         106 . The method of  claim 100 , wherein said hair loss is in the scalp or eyebrow of said subject. 
     
     
         107 . The method of  claim 100 , wherein said hair loss is in scarred skin tissue of said subject. 
     
     
         108 . The method of  claim 100 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         109 . The method of  claim 100 , wherein said step of disrupting is performed by exposing the region of said hair loss to a mechanical or chemical stimulus. 
     
     
         110 . The method of  claim 100 , wherein said step of disrupting is performed by exposing the region of said hair loss to radiation. 
     
     
         111 . The method of  claim 100 , wherein said administering step is via topical administration. 
     
     
         112 . The method of  claim 100 , wherein said administering step is via subepidermal administration. 
     
     
         113 . A method for generating a hair follicle in the dermis of a subject comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a compound or factor that upregulates sonic hedgehog (SHH) to said subject. 
     
     
         114 . The method of  claim 113 , wherein said factor that upregulates SHH is a fibroblast growth factor-9 polypeptide. 
     
     
         115 . The method of  claim 113 , wherein said subject has a reduced number of hair follicles as a result of androgenetic alopecia (AGA). 
     
     
         116 . The method of  claim 115 , wherein said AGA is male pattern baldness. 
     
     
         117 . The method of  claim 115 , wherein said AGA is female pattern baldness. 
     
     
         118 . The method of  claim 113 , wherein said subject has a reduced number of hair follicles as a result of a skin injury. 
     
     
         119 . The method of  claim 113 , wherein said subject has a reduced number of hair follicles in the scalp or eyebrow. 
     
     
         120 . The method of  claim 113 , wherein said subject has a reduced number of hair follicles in scarred skin tissue. 
     
     
         121 . The method of  claim 113 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         122 . The method of  claim 113 , wherein said step of disrupting is performed by exposing said region of hair loss to a mechanical or chemical stimulus. 
     
     
         123 . The method of  claim 113 , wherein said step of disrupting is performed by exposing the region of said hair loss to radiation. 
     
     
         124 . The method of  claim 113 , wherein said administering step is via topical administration. 
     
     
         125 . The method of  claim 113 , wherein said administering step is via subepidermal administration. 
     
     
         126 . A method for increasing the size of a hair follicle in the dermis of a subject comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a compound or factor that upregulates sonic hedgehog (SHH) to said subject. 
     
     
         127 . The method of  claim 126 , wherein said factor that upregulates SHH is a fibroblast growth factor-9 polypeptide. 
     
     
         128 . The method of  claim 126 , wherein said subject has reduced hair follicle size as a result of androgenetic alopecia (AGA). 
     
     
         129 . The method of  claim 128 , wherein said AGA is male pattern baldness. 
     
     
         130 . The method of  claim 128 , wherein said AGA is female pattern baldness. 
     
     
         131 . The method of  claim 126 , wherein said subject has reduced hair follicle size as a result of a skin injury. 
     
     
         132 . The method of  claim 126 , wherein said subject has reduced hair follicle size in the scalp or eyebrow. 
     
     
         133 . The method of  claim 126 , wherein said subject has reduced hair follicle size in scarred skin tissue. 
     
     
         134 . The method of  claim 126 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         135 . The method of  claim 126  wherein said step of disrupting is performed by exposing said region of hair loss to a mechanical or chemical stimulus. 
     
     
         136 . The method of  claim 126 , wherein said step of disrupting is performed by exposing the region of said hair loss to radiation. 
     
     
         137 . The method of  claim 126 , wherein said administering step is via topical administration. 
     
     
         138 . The method of  claim 126 , wherein said administering step is via subepidermal administration. 
     
     
         139 . A method for increasing hair follicle formation in the skin of a subject comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a compound or factor that upregulates sonic hedgehog (SHH) to said subject. 
     
     
         140 . The method of  claim 139 , wherein said factor that upregulates SHH is a fibroblast growth factor-9 polypeptide. 
     
     
         141 . The method of  claim 139 , wherein said subject has decreased hair follicle numbers as a result of androgenetic alopecia (AGA). 
     
     
         142 . The method of  claim 139 , wherein said subject has decreased hair follicle numbers as a result of a skin injury. 
     
     
         143 . The method of  claim 139 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         144 . The method of  claim 139 , wherein said step of disrupting is performed by exposing a region of said dermis of said subject comprising low hair follicle numbers to a mechanical or chemical stimulus or to radiation. 
     
     
         145 . The method of  claim 139 , wherein said administering step is via topical administration. 
     
     
         146 . The method of  claim 139 , wherein said administering step is via subepidermal administration. 
     
     
         147 . A method for treating, inhibiting, or suppressing a degenerative skin disorder comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a compound or factor that upregulates sonic hedgehog (SHH) to said subject. 
     
     
         148 . The method of  claim 147 , wherein said degenerative skin disorder is granuloma annulare. 
     
     
         149 . The method of  claim 147 , wherein said factor that upregulates SHH is a fibroblast growth factor-9 polypeptide. 
     
     
         150 . The method of  claim 147 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         151 . The method of  claim 147 , wherein said step of disrupting is performed by exposing said region of said degenerative skin disorder to a mechanical or chemical stimulus or to radiation. 
     
     
         152 . The method of  claim 147 , wherein said administering step is via topical administration. 
     
     
         153 . The method of  claim 147 , wherein said administering step is via subepidermal administration. 
     
     
         154 . A method for treating an androgenetic alopecia (AGA) in a scalp of a subject comprising the steps of (a) disrupting the epidermis in the region of said hair loss in said subject and (b) administering a composition comprising a compound or factor that upregulates sonic hedgehog (SHH) to said subject. 
     
     
         155 . The method of  claim 153 , wherein said factor that upregulates SHH is a fibroblast growth factor-9 polypeptide. 
     
     
         156 . The method of  claim 153 , wherein said step of administering is performed 3-12 days after said step of disrupting. 
     
     
         157 . The method of  claim 153 , wherein said step of disrupting is performed by exposing the region of said AGA to a mechanical or chemical stimulus or to radiation. 
     
     
         158 . The method of  claim 153 , wherein said administering step is via topical administration. 
     
     
         159 . The method of  claim 153 , wherein said administering step is via subepidermal administration.