Clinical Trial of Helminth-induced Immunomodulatory Therapy (HINT 2) in Relapsing-Remitting Multiple Sclerosis (P3.149)

OBJECTIVE: To explore the safety and preliminary effectiveness of the helminth Trichuris suis ova (TSO) (porcine whipworm) in subjects with early relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: The hygiene hypothesis suggests that the high level of sanitation in the modern environment (i.e., relative microbial deprivation) is one factor which may contribute to disordered immune regulation in putative autoimmune disorders, such as MS. DESIGN/METHODS: A baseline versus treatment design was employed in an exploratory clinical trial of 15 treatment naive, recently diagnosed RRMS subjects, each of whom underwent 5 months of pre-treatment observation and 10 months of treatment with TSO (2,500 live ova orally every two weeks). The primary outcome measures were 1) safety and tolerability of TSO and 2) changes in the number of gadolinium enhancing lesions (Gd+) during monthly brain MRI scans with double-dose gadolinium contrast which were read in random order by three masked radiologists. RESULTS: No significant safety or tolerability issues were observed. With 90% of timepoints analyzed to date, the mean number of Gd+ lesions per month was 3.2 during 5 months of observation and 2.1 during the last 5 months of treatment, a 34% relative reduction. Immunological assessments indicated that TSO was associated with increases in T regulatory cells and a modified Th2 immune response. Transcriptional analyses of peripheral blood mononuclear cells suggested that treatment led to diminished expression of the pellino E3 ubiquitin protein ligase 1 (pelli 1) gene, recently demonstrated to be a central activator of microglia in experimental autoimmune encephalomyelitis and possibly in MS itself. CONCLUSIONS: TSO appears safe and well-tolerated in RRMS subjects. The modest decrease observed in numbers of Gd+ lesions during treatment indicates that further studies if TSO will be required to assess its effectiveness in RRMS. Study Supported by: National Multiple Sclerosis Society Research Grant 3613A4/1 Disclosure: Dr. Fleming has nothing to disclose. Dr. Hartman has nothing to disclose. Dr. Maksimovic has nothing to disclose. Dr. Nace has nothing to disclose. Dr. Luzzio has nothing to disclose. Dr. Koehn has nothing to disclose. Dr. Ritter has nothing to disclose. Dr. Risa has nothing to disclose. Dr. Lawler has nothing to disclose. Dr. Maser has nothing to disclose. Dr. Mundt has nothing to disclose. Dr. Rolak has nothing to disclose. Dr. Cook has received personal compensation for activities with Biomarin, GlaxoSmithKline Inc., Zensun, Neuraltus, Merck & Co. Inc., and Advntrx. Dr. Field has nothing to disclose. Dr. Fabry has nothing to disclose.