Calcium-binding agents induce hair growth and/or nail growth

Abstract

This invention provides novel methods for inducing hair growth and/or inhibiting hair loss and/or inducing nail growth in a mammal. In various embodiments the methods involve administering, e.g., to a mammal in need thereof, a calcium-binding peptide and/or peptide-like moiety in an amount sufficient to induce hair growth and/or to inhibit hair loss. In certain embodiments the agent is topically and/or transdermally administered.

What is claimed is: 
     
         1 . A method of inducing bone or tooth demineralization in a mammal, said method comprising:
 administering to said mammal a calcium-binding peptide comprising one or more peptide domains said domain(s) comprising the sequence (X-Y-Z) n , wherein X is an amino acid selected from the group consisting of aspartic acid, glutamic acid, asparagine, alanine and glutamine or a conservative substitution thereof, Y and Z are amino acids independently selected from alanine, serine, threonine, phosphoserine, and phosphothreonine, or conservative substitutions thereof, and n is a number from 1 to 100; wherein when more than one of said domains is present the domains can be the same or different; and wherein said calcium-binding peptide moiety binds calcium phosphate;   wherein said calcium-binding peptide is administered in an amount sufficient to induce bone or tooth remineralization in said mammal.   
     
     
         2 . The method of  claim 1 , wherein said method comprises treating a tooth defect characterized by tooth demineralization in said mammal, wherein said administration results in tooth remineralization. 
     
     
         3 . The method of  claim 1 , wherein said method comprises treating a bone defect characterized by decreased bone density in said mammal, wherein said administration results in an increase in bone density. 
     
     
         4 . The method of  claim 1 , wherein said peptide comprises two or more of said domains joined by a non-peptide linker. 
     
     
         5 . The method of  claim 1 , wherein said peptide is a “D” peptide. 
     
     
         6 . The method of  claim 1 , wherein said peptide comprises one domain comprising the sequence (X-Y-Z) n , wherein X is an amino acid selected from the group consisting of aspartic acid, glutamic acid, asparagine, alanine and glutamine, Y and Z are amino acids selected from alanine, serine, threonine, phosphoserine, and phosphothreonine, and n is a number from 1 to 100. 
     
     
         7 . The method of  claim 6 , wherein said peptide or peptide domains comprise two or more copies of the amino acid sequence of a peptide subunit selected from the group consisting of Asp-Ala-Ala, Asp-Ala-Ser, Asp-Ala-Thr, Asp-Ala-pSer, Asp-Ala-pThr, Asp-Ser-Ala, Asp-Ser-Ser, Asp-Ser-Thr, Asp-Ser-pSer, Asp-Ser-pThr, Asp-Thr-Ala, Asp-Thr-Ser, Asp-Thr-Thr, Asp-Thr-pSer, Asp-Thr-pThr, Asp-pSer-Ala, Asp-pSer-Ser, Asp-pSer-Thr, Asp-pSer-pSer, Asp-pSer-pThr, Asp-pThr-Ala, Asp-pThr-Ser, Asp-pThr-Thr, Asp-pThr-pSer, Asp-pThr-pThr, Glu-Ala-Ala, Glu-Ala-Ser, Glu-Ala-Thr, Glu-Ala-pSer, Glu-Ala-pThr, Glu-Ser-Ala, Glu-Ser-Ser, Glu-Ser-Thr, Glu-Ser-pSer, Glu-Ser-pThr, Glu-Thr-Ala, Glu-Thr-Ser, Glu-Thr-Thr, Glu-Thr-pSer, Glu-Thr-pThr, Glu-pSer-Ala, Glu-pSer-Ser, Glu-pSer-Thr, Glu-pSer-pSer, Glu-pSer-pThr, Glu-pThr-Ala, Glu-pThr-Ser, Glu-pThr-Thr, Glu-pThr-pSer, Glu-pThr-pThr, Asn-Ala-Ala, Asn-Ala-Ser, Asn-Ala-Thr, Asn-Ala-pSer, Asn-Ala-pThr, Asn-Ser-Ala, Asn-Ser-Ser, Asn-Ser-Thr, Asn-Ser-pSer, Asn-Ser-pThr, Asn-Thr-Ala, Asn-Thr-Ser, Asn-Thr-Thr, Asn-Thr-pSer, Asn-Thr-pThr, Asn-pSer-Ala, Asn-pSer-Ser, Asn-pSer-Thr, Asn-pSer-pSer, Asn-pSer-pThr, Asn-pThr-Ala, Asn-pThr-Ser, Asn-pThr-Thr, Asn-pThr-pSer, Asn-pThr-pThr, Ala-Ala-Ala, Ala-Ala-Ser, Ala-Ala-Thr, Ala-Ala-pSer, Ala-Ala-pThr, Ala-Ser-Ala, Ala-Ser-Ser, Ala-Ser-Thr, Ala-Ser-pSer, Ala-Ser-pThr, Ala-Thr-Ala, Ala-Thr-Ser, Ala-Thr-Thr, Ala-Thr-pSer, Ala-Thr-pThr, Ala-pSer-Ala, Ala-pSer-Ser, Ala-pSer-Thr, Ala-pSer-pSer, Ala-pSer-pThr, Ala-pThr-Ala, Ala-pThr-Ser, Ala-pThr-Thr, Ala-pThr-pSer, Ala-pThr-pThr, Gln-Ala-Ala, Gln-Ala-Ser, Gln-Ala-Thr, Gln-Ala-pSer, Gln-Ala-pThr, Gln-Ser-Ala, Gln-Ser-Ser, Gln-Ser-Thr, Gln-Ser-pSer, Gln-Ser-pThr, Gln-Thr-Ala, Gln-Thr-Ser, Gln-Thr-Thr, Gln-Thr-pSer, Gln-Thr-pThr, Gln-pSer-Ala, Gln-pSer-Ser, Gln-pSer-Thr, Gln-pSer-pSer, Gln-pSer-pThr, Gln-pThr-Ala, Gln-pThr-Ser, Gln-pThr-Thr, Gln-pThr-pSer, and Gln-pThr-pThr. 
     
     
         8 . The method of  claim 1 , wherein n is a number from 2 to 8. 
     
     
         9 . The method of  claim 1 , wherein X is aspartic acid. 
     
     
         10 . The method of  claim 1 , wherein Y and Z are serine. 
     
     
         11 . The method of  claim 1 , wherein
 X is aspartic acid; and   Y and Z are serine.   
     
     
         12 . The method of  claim 11 , wherein said peptide comprises an amino acid sequence selected from the group consisting of 4DSS (SEQ ID NO:31), 5DSS (SEQ ID NO:22), 6DSS (SEQ 10 NO:32), 7DSS (SEQ ID NO:28), 8DSS (SEQ ID NO:33), 9DSS (SEQ ID NO:42), and 10DSS (SEQ ID NO:43). 
     
     
         13 . The method of  claim 11 , wherein said peptide consists of an amino acid sequence selected from the group consisting of 4DSS (SEQ ID NO:31), 5DSS (SEQ ID NO:22), 6DSS (SEQ 10 NO:32), 7DSS (SEQ ID NO:28), 8DSS (SEQ ID NO:33), 9DSS (SEQ ID NO:42), and 10DSS (SEQ ID NO:43). 
     
     
         14 . The method of  claim 1 , said peptide bears a protecting group. 
     
     
         15 . The method of  claim 1 , said peptide is not phosphorylated. 
     
     
         16 . A method of inducing hair growth or inhibiting hair loss and/or inducing nail growth in a mammal, said method comprising:
 administering to said mammal a calcium-binding peptide comprising one or more peptide domains said domain(s) comprising the sequence (X-Y-Z) n , wherein X is an amino acid selected from the group consisting of aspartic acid, glutamic acid, asparagine, alanine and glutamine or a conservative substitution thereof, Y and Z are amino acids independently selected from alanine, serine, threonine, phosphoserine, and phosphothreonine, or conservative substitutions thereof, and n is a number from 1 to 100; wherein when more than one of said domains is present the domains can be the same or different; and wherein said calcium-binding peptide moiety binds calcium phosphate;   wherein said calcium-binding peptide moiety is administered in an amount sufficient to induce hair growth and/or to inhibit hair loss, and/or to induce nail growth in said mammal.   
     
     
         17 . The method of  claim 16 , wherein said calcium-binding peptide is topically administered. 
     
     
         18 . The method of  claim 16 , wherein said method comprises inducing hair growth or inhibiting hair loss. 
     
     
         19 . The method of  claim 16 , wherein, wherein said method comprises inducing nail growth. 
     
     
         20 . The method of  claim 19 , wherein said administering comprises administering said calcium-binding peptide to a region selected from the group consisting of a nail, a nail bed, a cuticle, the coronet area of a hoof, the base of a horn. 
     
     
         21 . A method of identifying a tooth defect characterized by tooth demineralization in a subject, said method comprising:
 administering to said subject a calcium-binding peptide comprising one or more peptide domains said domain(s) comprising the sequence (X-Y-Z) n , wherein X is an amino acid selected from the group consisting of aspartic acid, glutamic acid, asparagine, alanine and glutamine or a conservative substitution thereof, Y and Z are amino acids independently selected from alanine, serine, threonine, phosphoserine, and phosphothreonine, or conservative substitutions thereof, and n is a number from 1 to 100; wherein when more than one of said domains is present the domains can be the same or different; and wherein said calcium-binding peptide moiety binds calcium phosphate, and where said calcium-binding peptide is attached to a detectable label; and   detecting said detectable label associated with a deminieralized tooth surface.   
     
     
         22 . A method of identifying a bone defect characterized by bone demineralization in a subject, said method comprising
 administering to said subject a calcium-binding peptide comprising one or more peptide domains said domain(s) comprising the sequence (X-Y-Z) n , wherein X is an amino acid selected from the group consisting of aspartic acid, glutamic acid, asparagine, alanine and glutamine or a conservative substitution thereof, Y and Z are amino acids independently selected from alanine, serine, threonine, phosphoserine, and phosphothreonine, or conservative substitutions thereof, and n is a number from 1 to 100; wherein when more than one of said domains is present the domains can be the same or different; and wherein said calcium-binding peptide moiety binds calcium phosphate, and where said calcium-binding peptide is attached to a detectable label; and   detecting said detectable label associated with a demineralized bone surface.