Modulating the effects of gamma-c-cytokine signaling for the treatment of alopecia and alopecia associated disorders
The γc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as alopecia and alopecia associated disorders. Compositions, methods, and kits to modulate signaling by at least one γc-cytokine family member for inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one alopecia related disorder are described.
1. A method of inhibiting, ameliorating, reducing a severity of, or treating at least one alopecia related disorder, the method comprising:
administering a composition comprising a pharmaceutically acceptable carrier and a γc cytokine antagonist peptide comprising a sequence comprising amino acids of γc box D-helix regions of at least two interleukin (IL) protein wherein the γc cytokine antagonist peptide comprises a core γc-box amino acid sequence that is 11 amino acids in length wherein the γc cytokine antagonist peptide comprises the sequence of SEQ ID NO: 1, wherein the γc cytokine antagonist peptide is administered in an amount sufficient to inhibit signaling by IL-2, IL-9, and/or IL-15, and/or decrease circulating levels of IL-6 and/or IFNγ to a subject in need thereof,
thereby inhibiting, ameliorating, reducing a severity of, or treating alopecia and/or immune-mediated hair loss.
2. The method of claim 1 , wherein the γc cytokine antagonist peptide consists of the sequence of SEQ ID NO: 1.
3. The method of claim 1 , wherein the γc cytokine antagonist peptide comprises 19 to 50 amino acids.
4. The method of claim 1 , wherein the γc cytokine antagonist peptide further comprises a conjugate at the N-termini, C-termini, side residues, or a combination thereof.
5. The method of claim 4 , wherein the conjugate comprises one or more additional moieties selected from the group consisting of bovine serum albumin (BSA), albumin, Keyhole Limpet Hemocyanin (KLH), Fc region of IgG, an antibody against a cell-specific antigen, a receptor, a ligand, a metal ion, and Poly Ethylene Glycol (PEG).
6. The method of claim 1 , wherein the γc cytokine antagonist peptide further comprises a hydrocarbon linker element.
7. The method of claim 1 , wherein the composition is formulated for topical, oral, or parenteral delivery.