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Compositions and methods for regulating hair growth

A technology of hair growth and composition, applied in the field of hair growth regulating composition, capable of solving problems such as identifying active targets of minoxidil

Active Publication Date: 2015-05-06
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Active targets of minoxidil in AGA treatment have not been conclusively identified

Method used

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  • Compositions and methods for regulating hair growth
  • Compositions and methods for regulating hair growth
  • Compositions and methods for regulating hair growth

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0147] PTGDS and PGD2 are elevated in bald scalp

[0148] To assess total gene expression changes in the bald scalp of men with AGA, we performed gene expression microarrays in 5 men with AGA, comparing bald scalp to hairy scalp. The correlation coefficients between replicates with hairy scalp and between replicates with bald scalp were close to 1 ( figure 1 A). The intra-individual correlation coefficient for haired versus bald scalp was also close to 1, indicating the advantage of paired samples as internal controls. We identified 250 transcripts that were differentially expressed in human hairy versus bald scalp. As evidence of the validity of these transcripts, the clustering algorithm classifies samples as hairy or bald based on the expression of these genes ( figure 1 B). Hair keratin was upregulated in the haired scalp, as expected. For unclear reasons, hemoglobin-related transcripts are elevated in bald scalp. In haired scalp, 169 genes were elevated, and 81 ...

Embodiment 2

[0151] Non-permanent hair follicle mouse keratinocytes express Ptgds at the end of anagen

[0152] To better understand the normal biological function of Ptgds and PGD2 on hair growth, we took advantage of the well-characterized, synchronized hair cycle in mice. Fluctuations in gene expression and protein levels could be traced to different stages of the hair follicle cycle by examining the skin at different ages or after depilation of mouse hair, which induces a synchronized new hair follicle cycle. In the course of studying the characteristics of the synchronized mouse hair cycle, we demonstrated the phase of the hair cycle relative to postnatal (PN) days in mouse skin biopsy samples. We are confident that the histological features of mice at PN21 are those of late telogen, PN35 late anagen, and PN46 catagen, as suggested by macroscopic appearance. As measured by qPCR, Ptgds mRNA peaked in the late phase of anagen and was 7-fold higher than the telogen (telogen) phase of ...

Embodiment 3

[0156] Expression of PTGDS in non-permanent keratinocytes of human hair follicles

[0157] In normal terminal human hair follicles, we found a similar presence of PTGDS, mainly in non-permanent hair follicles below the arrector pili muscle ( Figure 4 A). However, staining is variable, and many normal human hair follicles exhibit minimal or no staining ( Figure 4 B). This is consistent with lower PTGDS mRNA levels in haired versus bald scalps, and may also reflect a lack of synchrony in the human hair follicle cycle. In the miniaturized hair follicles of the bald human scalp, outside the bulge ( Figure 4 , C and E) and in some cases inside the upper base bulge ( Figure 4 D) Sebaceous gland and follicle keratinocytes express PTGDS. We also detected PTGDS outside the hair follicle epithelium, indicating a potential source of PGD2 in the dermis ( Figure 4 , E and F). In hair follicles undergoing catagen, PTGDS is present in mast cells within the fibrous band, the for...

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Abstract

The invention relates to compositions and methods for regulating hair growth. Specifically, the invention relates to regulating hair growth by regulating the activity one of the prostaglandin D2 (PGD2) receptors, DP-2 (GPR44). Compositions and methods for regulating hair growth include inhibiting hair growth by administering a DP-2 agonist, or stimulating hair growth by administering a DP-2 antagonist.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Patent Application 61 / 613,829, filed March 21, 2012, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to compositions and methods for regulating hair growth. In particular, the present invention relates to the regulation of hair growth by modulating the activity of DP-2 (GPR44), one of the prostaglandin D2 (PGD2) receptors. Background technique [0004] Eighty percent of Caucasian men experience some degree of androgenetic alopecia (AGA) before the age of 70. Testosterone is required for the development of AGA, and a genetic predisposition locus in the androgen receptor is present in a minority of men with AGA; however, additional factors contributing to the disorder remain unknown. Research on AGA has the potential to provide insight into other androgen-mediated diseases such as benign prostatic hyper...

Claims

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Application Information

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IPC IPC(8): A61Q7/00A61Q7/02
CPCA61Q7/00A61Q7/02A61K8/365A61K8/492A61K2800/78A61K2800/782G01N33/88G01N2500/02A61K31/473A61K31/506A61K8/49A61K8/69A61K45/06A61K31/403A61K31/437A61K31/58A61K31/191A61P17/00A61P17/14A61P43/00A61K2300/00
Inventor G·科特萨雷利斯G·菲茨杰拉德L·卡萨
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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