Modulating the effects of gamma-c-cytokine signaling for the treatment of alopecia and alopecia associated disorders
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Publication Number
US-12030936-B2
Publication Date
2024-07-09
Expiration Date
Abstract
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.
Core Innovation
The invention relates to inhibiting, ameliorating, reducing the severity of, or treating alopecia and/or immune-mediated hair loss by modulating γc cytokine signaling. It uses a γc cytokine antagonist peptide delivered as a composition together with a pharmaceutically acceptable carrier, where the peptide comprises amino acids of γc box D-helix regions of at least two interleukin proteins and includes a core γc-box amino acid sequence that is 11 amino acids in length and comprises the sequence of SEQ ID NO:1.
The disclosed γc antagonist peptide is illustrated with BNZ-γc and peptide modification options that include conjugates at N-termini, C-termini, and/or side residues, together with moieties such as PEG, BSA, KLH, or Fc. The document also describes the possibility of adding intra-peptide hydrocarbon linker elements and peptide length constraints of 19 to 50 amino acids.
In immune-mediated hair loss and GvHD models, BNZ-γc is described as inhibiting IL-15/IL-9 activity, reducing IL-6 and IFNγ, improving survival, and supporting hair regrowth. The biological rationale includes humanized NSG mouse and cellular data, and the work links IL-15/Jak3/STAT5 signaling and NKG2A+ CD8+ T-cells to disease.
Claims Coverage
The claims include one independent claim directed to treating alopecia and/or immune-mediated hair loss by administering a γc cytokine antagonist peptide, with dependent claims refining peptide identity, length, conjugation, moieties, and delivery routes. The independent claim centers on a pharmaceutically acceptable composition containing a γc cytokine antagonist peptide with a defined 11-amino-acid core sequence (SEQ ID NO:1) and activity against IL-2, IL-9, and/or IL-15 signaling and/or reduction of IL-6 and/or IFNγ levels.
γc cytokine antagonist peptide composition for alopecia treatment
Administering a composition comprising a pharmaceutically acceptable carrier and a γc cytokine antagonist peptide comprising amino acids of γc box D-helix regions of at least two interleukin proteins, where the peptide comprises a core γc-box amino acid sequence that is 11 amino acids in length and includes SEQ ID NO:1, and 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.
Specific peptide sequence of SEQ ID NO:1
The method uses a γc cytokine antagonist peptide having the amino acid sequence of SEQ ID NO:1.
Peptide length constraint (19 to 50 amino acids)
The method is carried out using a γc cytokine antagonist peptide consisting of 19 to 50 amino acids.
Peptide conjugation at termini and/or side residues
The γc cytokine antagonist peptide additionally comprises a conjugate at one or more locations: the N-termini, C-termini, and/or side residues.
Conjugate includes specified moieties
The conjugate includes additional moieties selected from bovine serum albumin, albumin, Keyhole Limpet Hemocyanin, the Fc region of IgG, an antibody against a cell-specific antigen, a receptor, a ligand, a metal ion, and Poly Ethylene Glycol.
Topical, oral, or parenteral formulation
The composition is formulated for topical, oral, or parenteral delivery.
The claim set covers administration of a γc cytokine antagonist peptide centered on a core γc-box region defined by SEQ ID NO:1 to inhibit IL-2, IL-9, and/or IL-15 signaling and/or decrease IL-6 and/or IFNγ, thereby treating alopecia and/or immune-mediated hair loss, with dependent claims narrowing peptide length, conjugation, specified moieties, and delivery routes.
Stated Advantages
Inhibiting, ameliorating, reducing a severity of, or treating alopecia and/or immune-mediated hair loss.
Inhibiting signaling by IL-2, IL-9, and/or IL-15.
Decreasing circulating levels of IL-6 and/or IFNγ.
Improving survival.
Supporting hair regrowth.
Documented Applications
Treatment of alopecia and/or immune-mediated hair loss.
Immune-mediated hair loss and graft-versus-host disease models.
Modeling immune-mediated alopecia and systemic GvHD in humanized NSG mice.
Treating immune-mediated diseases including vitiligo, psoriasis, pemphigus/pemphigoid, and GvHD.
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