Trichuris Suis Ova (TSO) As an Immune-Inflammatory Treatment for Repetitive Behaviors in ASD

Friday, May 15, 2015: 11:30 AM-1:30 PM
Imperial Ballroom (Grand America Hotel)
E. Hollander1, C. J. Ferretti2, B. P. Taylor3, R. Noone4, E. Racine4 and E. Doernberg4, (1)Dept. of Psychiatry and Behavioral Sciences, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, (2)Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, (3)Dept. Of Psychiatry and Behavioral Sciences, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, (4)Psychiatry, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
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, specifically 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.

Objectives:  To assess the effect of TSO vs placebo on irritability, repetitive behaviors and global functioning in adults with ASD. 

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.  ASD diagnosis was confirmed by DSM-IV criteria supported by the ADOS.  Subjects had a personal/family history of allergies, baseline Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of ≥ 6 and an IQ ≥70. Eligible subjects returned every two weeks to receive 2500 TSO ova, and to complete subject, parent (Aberrant Behavior Checklist [ABC], Social Responsiveness Scale [SRS], Repetitive Behavior Scale-Revised [RBS-R]) and clinician (Y-BOCS) assessments in addition to safety monitoring, clinical labs and stool sampling.  

Results:  This exploratory safety and efficacy study to determine effect sizes for future trials included young adults with high functioning ASD, normal intelligence and good verbal skills.  Scores on the ABC-Irritability subscale were low at baseline.  Patients demonstrated improvement in the repetitive behavior domain.  Large effect sizes were seen on (1) the Montefiore-Einstein Rigidity Scale (MERS), a scale of behavioral rigidity, (d = 0.79); (2) the RBS-R Sameness Behavior subscale (d = 1.0) and (3) the RBS-R Restricted Behavior subscale (d = 0.82).  There was also a large effect size on the ABC – Irritability subscale (d=0.78).  No changes were observed in the social communication domain of ASD. As in previous studies of TSO, the side effect profile is low.  

Conclusions:  The results of our proof of concept pilot study demonstrate the feasibility of completing a 28 week study of TSO in an ASD population, the safety of TSO in this population, and the potential efficacy, with moderate to large effect sizes, for improvement in repetitive behaviors/ rigidity and irritability in patients. TSO was tolerated well by subjects, with mild limited side effects which resolved without medication or action taken to the study drug.  Flatulence, stomach cramping and nausea/vomiting were more common with TSO, while loose stool, weight loss and knee pain were more common with placebo.

 Funding provided by the Simons Foundation.  Drug /Placebo provided by Coronado Biosciences.