Trichuris Suis Ova in Autism Spectrum Disorders

Autism is a pervasive developmental disorder affecting social, communicative, and
compulsive/repetitive behaviors. It is also frequently accompanied by aggression,
self-injury, and irritability, making care for these individuals a significant challenge for
families or institutional settings. Currently risperidone is the only medication approved by
the Food and Drug Administration (FDA) for irritability associated with autism, although not
all patients respond to risperidone or are able to tolerate its side effects. As such,
additional targeted treatments need to be explored in autism. Neuroimmune disturbance has
been demonstrated in patients with autism (Ashwood et al., 2006; DelGuidice, 2003) and the
presence of neuroinflammation may play a role in initiating or maintaining CNS dysfunction
characteristic of the disorder (Pardo et al, 2005). Therefore, there is considerable interest
in using immunomodulatory medications to address core and associated symptoms.

Trichuris suis ova (TSO) are the eggs of intestinal helminthes which induce Th2 cytokine
release and nonspecifically downregulate Th1 responsiveness (Summers et al., 2003). Treatment
with TSO has been shown to have a beneficial effect in autoimmune inflammatory bowel disease
(Summers et al, 2003; Summers et al., 2005a; Summers et al., 2005b) and anecdotal reports
from patients with autism have demonstrated that TSO may be effective in reducing repetitive
behaviors, aggression, self-injury, and impulsivity.

To date, many medications have been used in individuals with autism and the history of
psychopharmacology of autism is notable for the exaggerated benefit of a variety of
treatments. To date, most medication studies in the field have been open-label without use of
a placebo control and without systematic behavioral assessments. The current practice of
prescribing medications to patients with autism without scientifically demonstrated efficacy
underscores the necessity for methodologically rigorous studies to be conducted.

We propose a double blind placebo-controlled crossover trial of TSO, where subjects would be
randomized to receive placebo or TSO for 12 weeks, with a 4 week washout and then 12 weeks of
the the treatment not yet received. To assess the effect on social cognition, repetitive
behaviors, aggression and irritability, and global functioning in adults with autism spectrum
disorder. The objectives of the proposed study are to develop an innovative treatment
approach to autism by 1) assessing the safety and efficacy of TSO treatment using behavioral
and laboratory outcome measures; 2) determining whether this treatment has sufficient promise
to warrant consideration of a larger, multi-centered, placebo-controlled clinical trial; 3)
conducting secondary analyses to explore the relationship between clinical features, immune
mechanisms, and treatment response.

Inclusion Criteria:

1. Age 18-35, inclusive, at the time of consent

2. Outpatient

3. Meet criteria for the diagnosis of Autism Spectrum Disorder according to the
DSM-IV-TR, and supported by the ADOS or ADI-R.

4. Have an IQ of 70 or greater

5. Participants who are taking other medications prior to enrollment must be on a stable
dose of concomitant medication, including psychotropic, anticonvulsant, or sleep aid
for at least 3 months prior to baseline ratings

6. Be judged reliable for medication compliance and agree to keep appointments for study
contacts and tests as outlined in the protocol (both subjects and guardians)

7. Have a personal or family history of allergies.

Exclusion Criteria:

1. History of Bipolar disorder or Psychotic Disorders (e.g. schizophrenia or
schizoaffective disorders).

2. Previous diagnosis of Rett's Disorder or Childhood Disintegrative Disorder

3. Uncontrolled seizure disorders (seizures within the past 6 months)

4. Pregnant or breast feeding at screening, or at any time during the study

5. Chronic medical illness that would interfere with or contraindicate participation in
the study, or clinically significant abnormalities in baseline laboratory testing or
physical exam.

6. Treatment in the last 12 weeks with cyclosporine, methotrexate, infliximab or
immunomodulatory agents

7. Treatment in the last 2 weeks with antibiotics, antifungal or antiparasitic
medications

8. Presence of any organic or systemic disease or need for a therapeutic intervention,
which would confound the interpretation of results.

9. History of previous treatment with Trichuris Suis Ova (TSO).