RTL therapy for multiple sclerosis: a Phase I clinical study.
A human recombinant T cell receptor ligand (RTL1000) consisting of DR2 α1 and β1 domains linked covalently to MOG-35-55 peptide can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE), and was evaluated for safety in a Phase 1 randomized, placebo-controlled, escalating dose study in 34 subjects with multiple sclerosis (MS). RTL1000 was safe and well tolerated at a dose of ≤60 mg that is well within the effective dose range for EAE and did not cause worsening of MS disease at doses ≤200 mg. RTL1000 represents a novel approach for the treatment of MS that promises potent immunoregulation and CNS repair without global immunosuppression.
Neuroimmunology Research, Veterans Affairs Medical Center, 3710 SW US Veterans' Hospital Rd., Portland, OR 97239, United States. offnerva@ohsu.edu
Halina
H
Offner
Sushmita
S
Sinha
Gregory G
GG
Burrows
Adolph J
AJ
Ferro
Arthur A
AA
Vandenbark
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D017433:Protein Structure, Secondary; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use
C542328:RTL1000 protein; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins