TRICHURIS SUIS OVA (TSO) AS AN IMMUNE-INFLAMMATORY TREATMENT FOR REPETITIVE BEHAVIORS IN ASD

abstract Background Inflammatory mechanisms have been implicated in Autism Spectrum Disorders (ASD) and immunomodulatory interventions, such as Trichuris Suis Ova (TSO), may be an experimental therapeutic option. ASD patients have dampened Th2 anti-inflammatory cytokine response, and increased Th1 proinflammatory cytokine response, and some improve in response to fever, suggesting a possible role of immune-inflammatory factors. Helminth worms, such as TSO, have been studied in autoimmune disorders in part from the hygiene hypothesis, which suggests that a rise in hygiene is associated with less protective microbes in humans and an increase in autoimmune inflammatory disorders and that stimulation of the immune system by microbes is protective against the development of inflammatory diseases. Methods A 28 week double-blinded, randomized crossover study of TSO vs. placebo in 10 adults, aged 17.5 to 35, with ASD was completed, with a 4 week washout period between each 12 week phase. Subjects had a personal/family history of allergies, baseline YBOCS score of≥6 and an IQ ≥70. Eligible subjects received 2500 TSO ova every 2 weeks and completed subject, parent and clinician assessments, in addition to safety monitoring, clinical labs and stool sampling. Parent-rated measures included the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Repetitive Behavior Scale- Revised (RBS-R). Clinician rated measures included the Montefiore-Einstein Rigidity Scale (MERS) and the Yale-Brown Obsessive Compulsive Scale (YBOCS). Results This exploratory safety and efficacy study included young adults with high functioning ASD, normal intelligence and good verbal skills. Irritability scores on the ABC-I were low at baseline. Of interest, measures of rigidity, craving for sameness and restricted interests, distinct domains of repetitive behaviors, were noted to improve in patients on TSO vs placebo, with large effect sizes. These changes were observed on the MERS (d=0.79), RBS-R Sameness Subscale (d =1.0) and RBS-R Restricted Subscale (d=0.82). There were also improvements on the YBOCS Compulsion Subscale (d=0.52) and the ABC-Irritability Subscale (d =0.78). The side effect profile was low. Throughout the study only minimal gastrointestinal distress was observed in some patients. Conclusion This is the first placebo controlled trial of TSO in an ASD population. Our exploratory pilot study demonstrates the feasibility of completing a 28 week study of TSO in an ASD population, safety of TSO in this population, and potential efficacy for rigidity, insistence of sameness, and repetitive/restricted behaviors. TSO was tolerated well by subjects, with mild, limited side effects which resolved without medication or action taken to the study drug. Limitations of the trial included a small sample size, lack of irritability at baseline, and use of parent outcomes measures in this population that potentially impact our understanding of the results. Future studies are needed to replicate these preliminary findings in a younger population stratified for higher baseline irritability, and further exploration of target engagement with the immune system and relationship to clinical improvement in ASD.