Case study

Effect of pioglitazone treatment on behavioral symptoms in autistic children

Marvin Boris¹ , Claudia C Kaiser² , Allan Goldblatt¹ , Michael W Elice¹ , Stephen M Edelson³ , James B Adams⁴ and Douglas L Feinstein²

¹  77 Froehlich Farm Blvd Woodbury, New York 11797, USA

²  Department of Anesthesiology, University of Illinois, Chicago, IL, 60612, USA

³  Autism Research Institute, 4182 Adams Ave, San Diego, CA 92116, USA

⁴  Arizona State University, PO Box 876006, Tempe, AZ 85287-6006, USA

author email corresponding author email

Journal of Neuroinflammation 2007, 4:3doi:10.1186/1742-2094-4-3

Published:	5 January 2007

Abstract

Introduction

Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARγ), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism.

Case description

The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment.

Discussion and evaluation

In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients.

Conclusion

Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.