Methods and compositions for alopecia treatment using fibroblasts and fibroblast-derived products

Patent metadata

Field	Value
Publication number	US-2024139257-A1
Application number	US-202218561979-A
Country	US
Kind code	A1
Filing date	May 25, 2022
Priority date	May 26, 2021
Publication date	May 2, 2024
Grant date	—

Abstract

Disclosed herein are methods and compositions for treatment and prevention of alopecia, including alopecia areata. Aspects are directed to methods for stimulating or accelerating hair follicle regeneration. Certain aspects are directed to methods for treating alopecia areata comprising administration of fibroblasts and/or a fibroblast derived product to a subject suffering from alopecia areata. In some cases, a fibroblast derived product is conditioned media, exosomes, or apoptotic bodies from fibroblasts, formulated for topical use for treatment or prevention of alopecia areata.

First claim

What is claimed is:

1 . A method of treating or preventing alopecia in a subject comprising providing to the subject an effective amount of fibroblasts or fibroblast-derived products.

2 . The method of claim 1 , wherein the alopecia is associated with dermal inflammation.

3 . The method of claim 1 or 2 , wherein the alopecia is alopecia areata.

4 . The method of claim 1 , wherein the alopecia is androgenetic alopecia.

5 . The method of claim 4 , wherein the androgenetic alopecia is male-pattern hair loss.

6 . The method of claim 4 , wherein the androgenetic alopecia is female-pattern hair loss.

7 . The method of any of claims 1 - 6 , wherein the fibroblasts or fibroblast-derived products are administered topically.

8 . The method of any of claims 1 - 6 , wherein the fibroblasts or fibroblast-derived products are administered intradermally and/or transdermally.

9 . The method of any of claims 1 - 8 , wherein the fibroblasts or fibroblast-derived products are administered to a region of the scalp of the subject.

10 . The method of claim 9 , further comprising administering a regenerative light source to the region of the scalp of the subject.

11 . The method of any of claims 1 - 10 , wherein the method comprises providing to the subject an effective amount of fibroblasts.

12 . The method of claim 11 , wherein the fibroblasts are allogeneic, xenogeneic, or autologous to the subject.

13 . The method of claim 11 or 12 , wherein the fibroblasts are derived from skin, adipose, bone marrow, omental tissue, blood, deciduous teeth, fallopian tubes, testicular tissue, ovarian tissue, hair follicle, endometrial tissue, or a combination thereof.

14 . The method of any of claims 11 - 13 , wherein the fibroblasts are dermal fibroblasts.

15 . The method of any of claims 11 - 14 , wherein the fibroblasts were previously subjected to conditions sufficient to enhance regenerative activity.

16 . The method of claim 15 , wherein the conditions are sufficient to upregulate HIF1α expression in the fibroblasts.

17 . The method of claim 16 , wherein the conditions are sufficient to upregulate HIF1α by at least 25% relative to an untreated control.

18 . The method of any of claims 11 - 14 , wherein the conditions are sufficient to enhance nuclear translocation of HIF1α in the fibroblasts.

19 . The method of any of claims 11 - 18 , wherein the conditions comprise agents capable of imitating hypoxia.

20 . The method of any of claims 11 - 19 , wherein the conditions comprise culturing the fibroblasts with carbon monoxide.

21 . The method of claim 20 , wherein the conditions comprise exposing the fibroblasts to a gas composition comprising between about 0% and about 79% nitrogen by weight, between about 21% and about 99.999999% oxygen by weight, and between 0.0000001% and about 0.3% carbon monoxide by weight.

22 . The method of claim 21 , wherein the gas composition comprises 0% nitrogen and about 99.999999% oxygen.

23 . The method of any of claims 20 - 22 , wherein the gas composition comprises between about 0.005% and about 0.05%.

24 . The method of any of claims 11 - 23 , wherein the fibroblasts were previously subjected to conditions sufficient to enhance survival and/or activity of the fibroblasts.

25 . The method of claim 24 , wherein the conditions comprise treatment with an epigenetic modulator.

26 . The method of claim 25 , wherein the epigenetic modulator is a histone deacetylase inhibitor.

27 . The method of claim 26 , wherein the histone deacetylase inhibitor is valproic acid, vorinostat, entinostat, panobinostat, trichostatin A, mocetinostat, belinostat, FK228, MC1568, tubastatin, sodium butyrate, or sulforaphane.

28 . The method of claim 25 , wherein the epigenetic modulator is a DNA methyltransferase inhibitor.

29 . The method of claim 28 , wherein the DNA methyltransferase inhibitor is 5-azacytidine.

30 . The method of claim 24 , wherein the conditions comprise culturing the fibroblasts with GSK-3 inhibitor.

31 . The method of claim 30 , wherein the GSK-3 inhibitor is lithium or a lithium salt.

32 . The method of any of claims 1 - 10 , wherein the method comprises providing to the subject an effective amount of fibroblast-derived products.

33 . The method of claim 32 , wherein the fibroblast-derived products were obtained from fibroblasts derived from skin, adipose, bone marrow, omental tissue, blood, deciduous teeth, fallopian tubes, testicular tissue, ovarian tissue, hair follicle, endometrial tissue, or a combination thereof.

34 . The method of claim 33 , wherein the fibroblast-derived products were obtained from dermal fibroblasts.

35 . The method of any of claims 32 - 34 , wherein the fibroblast-derived products were obtained from fibroblasts that are allogeneic, xenogeneic, or autologous to the subject.

36 . The method of any of claims 32 - 35 , wherein the fibroblast-derived products comprise conditioned media from culture of fibroblasts.

37 . The method of claim 36 , wherein the conditioned media was obtained from culture of the fibroblasts in EMEM, alpha-MEM, IMDM, DMEM, or RPMI.

38 . The method of claim 36 or 37 , wherein the conditioned media was generated by culture of adherent fibroblasts in a liquid suspension comprising nutrition for the fibroblasts.

39 . The method of claim 38 , wherein the liquid suspension comprises a growth factor.

40 . The method of claim 38 or 39 , wherein the liquid suspension comprises stem cell exosomes.

41 . The method of claim 40 , wherein the stem cell exosomes are exosomes from mesenchymal stem cells.

42 . The method of claim 41 , wherein the mesenchymal stem cells were derived from umbilical cord, bone marrow, skin, fallopian tube, adipose tissue, endometrial tissue, peripheral blood, menstrual blood, hair follicle, or a combination thereof.

43 . The method of any of claims 38 - 42 , wherein the liquid suspension comprises a neutralizing factor capable of inhibiting activity of one or more inflammatory mediators.

44 . The method of claim 43 , wherein the neutralizing factor is a monoclonal antibody, an antisense oligonucleotide, or a gene editing system.

45 . The method of claim 43 or 44 , wherein the neutralizing factor is an antibody capable of binding to interleukin-1, interleukin-6, interleukin-8, interleukin-9, interleukin-11, interleukin-12, interleukin-15, interleukin-17, interleukin-18, interleukin-21, interleukin-23, interleukin-27, interleukin-33, TNFα, interferon gamma, TNFβ, or lymphotoxin.

46 . The method of any of claims 38 - 45 , wherein the liquid suspension comprises VEGF, EGF, PGDF-BB, IGF-1, HGF-1, NGF, BDNF, IL-3, IL-4, IL-10, IL-13, IL-20, IL-35.

47 . The method of any of claims 32 - 35 , wherein the fibroblast-derived products are microvesicles from fibroblasts.

48 . The method of any of claims 32 - 35 , wherein the fibroblast-derived products are exosomes from fibroblasts.

49 . The metho

Assignees

• Figene Llc

Inventors

• Ichim Thomas
• O'Heeron Pete

Classifications

• A61K35/33 Primary

  Fibroblasts · CPC title

• A61K31/122

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title

• A61N5/0617

  Hair treatment · CPC title

• A61P17/14 Primary

  for baldness or alopecia · CPC title

• C12N5/0656

  Adult fibroblasts · CPC title