title: Immunosuppressive activity of a novel peptide analog of α-melanocyte stimulating hormone (α-MSH) in experimental autoimmune uveitis.
abstract: Autoimmune uveitis is an inflammatory disorder of the eye that can lead to pain and vision loss. Steroids and immunosuppressive drugs are currently the only therapeutics for uveitis and have serious ocular and systemic toxicities. Therefore, safer alternative therapeutics are desired. Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide that suppresses effector T cell functions, induces regulatory T cells and has beneficial effects in certain autoimmune and transplant models. A novel d-amino acid peptide analog of native α-MSH (dRI-α-MSH) was produced that was protected from protease digestion and had increased selectivity for the melanocortin-1 receptor. Systemic delivery of the dRI-α-MSH analog dramatically suppressed disease progression and retained retinal architecture in the experimental autoimmune uveitis (EAU) model. Local delivery by periorbital injection was equally effective. Importantly, treatment with the novel dRI-α-MSH analog suppressed uveitis with a similar magnitude to the corticosteroid, dexamethasone. Data indicate that the novel dRI-α-MSH analogs show anti-inflammatory activities and have potential therapeutic use in uveitis and other autoimmune diseases.
authors.affiliation: Transplant and Immune Mediated Diseases, Genzyme Corporation, Framingham, MA 01701, USA. andrea.edling@genzyme.com
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Edling
authors.forename: Danilo
authors.initials: D
authors.lastname: Gomes
authors.forename: Timothy
authors.initials: T
authors.lastname: Weeden
authors.forename: John
authors.initials: J
authors.lastname: Dzuris
authors.forename: Jim
authors.initials: J
authors.lastname: Stefano
authors.forename: Clark
authors.initials: C
authors.lastname: Pan
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.forename: Johanne
authors.initials: J
authors.lastname: Kaplan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Perricone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000627:therapeutic use; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D000521:alpha-MSH