New Perrpectirem in Treetmeat of MS: Reaultm with recombhant Interferon beta-la

HUMAN RECOMBINANT INTERFERON BETA IN THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

C. Fieschi

Dept. Neural Sci. University of Rome “La Sapienza”

An open, randomised trial with recombinant hllnun Interferon beta (r-hIFN-beta) involving 72 patients with clinically definite and/or laboratory supported relapsing/remitting Multiple Sclerosis has been performed at the University “La Sapienza” and al the S. Camillo Hospital of Rome. After a 6 month period of clinical and MRI observation (baseline findings), patients were randomly assigned to either 2 treatment groups receiving 3 MIU o 9 MIU respectively of recombinant human IFN beta (r-hlFN-beta) self-administered by subcutaneous injection three times a week for 6 months. All patients were examined by MRI with and without gadolinium (Gd-DTPA) elrery 4 weeks for the entire duration of the study (12 months). The main aim of the study was to test the hypothesis that r-hlFN-beta may halt or slow the progression of the disease by showing a significant reduction in MRI activity. This will be achieved by comparing pre and post- treatment periods. As additional clinical endpoint, the exacerbation rate during these two periods will be compared. This study began in June 1993 and the final analysis of MRI data has been completed on Spring 1995. Clinical and MRI findings will be presented at the meeting

TREATMENT OF MULTIPLE SCLEROSIS AND OTHER AUTOIMMUNE DISEASES BY ORAL TOLERANCE TO AUTOANTIGENS

Howa d L. Weiner Marika J. Hohol, Hikoaki Fukaura, Sally Kent, *E. John &av. Samia J: Khoury and David A. Hailer. Center for Neurologic Diseases and *Section of Clinical Epidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston. MA, USA.

Or;rlij adminiatzcd autoantigcna aupprcss animal models of autoimmunity, including EAE, collagen and adjuvant -induced arthritis, uveitis and diabetes in the NOD mouse. Oral antigen induces different mechanisms of tolerance depending on dose, with low doses favoring active suppression and high doses favoring anergy or deletion. Active suppression in oral tolerance involves the generation of antigen-specific regulatory cells in the gut which act by releasing down-regulatory cytokines such as TGF-P and IL-4 at the target organ. Thus, one can suppress inflammation at a target organ hy orally administering an antigen from the site of inflammation, even if it is not the target of the autoimmune response. A pilot study of oral tolerance in MS patients demonstrated no toxicity and suggested differential responses in subgroups based on DR phenotype or sex. Based on this pilot trial a double-blind placebo controlled muhi-centered trial of oral myelin (Myloral) in 504 relapsing- remitting patients is in progress with prospective randomization for DR type and sex. Sixteen patients initially treated in the pilot study have continued to receive oral myelin for as long a five years in an open label continuation study. Immunologic analysis of these patients demonstrates increased MBP and PLP specific TFG-p secreting cells compared to nod- fed MS patients with no change in MBP or PLP specific IFN-1 secreting cells, There was no increase in tetanus toxoid secreting TGF-P cells in fed paGents. Clinically, there was a positive correlation between worsening EDSS during the open-label study and being off oral myelin. The annual relapse rate in the two years prior to treatment was I .6 and subsequently was 0.5. The average EDSS of patients was unchanged at 3 years. No toxicity was ahsent. If positive clinical results are seen in the current phase III trial, oral myclin could be initiated early in the disease process and given in combination with other drugs. Recent clinical trials also have shown positive effects of low dose oral collagen in rheumatoid arthritis and clinical trials are in progress feeding S antigen in uveitis and clinical trials of oral insulin in juvenile diabetes are planned.

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