Untitled

Abstract

IntroductionAutism 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 descriptionThe 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 evaluationIn 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.ConclusionPioglitazone should be considered for further testing of therapeutic potential in autistic patients.

Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

“…Furthermore, Adams and coworkers have comprehensively reviewed the link between autism and metabolic disturbances in young and adult autistic patients [25]. Interestingly, another study showed that treatment of autism patients with pioglitazone resulted in improvement of some symptoms, with a stronger effect in younger patients [26]. This is the first report showing that changes in these molecules occur in an age-dependent manner in ASD individuals.…”

Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates

“…For example, MIA mouse offspring treated with antipurinergic therapy (APT) (69, 70) or the gut bacterium Bacteroides fragilis (62) exhibit improved behavioral outcomes. Future studies are needed to explore emerging clinical (114) and preclinical (68, 73, 115) treatments targeting the immune system as a promising area of research for ASD drug discovery efforts.…”

Modeling Autistic Features in Animals

“…A preliminary study of the thiazolidinedione, pioglitazone, which has anti-inflammatory properties, causes a significant decrease in irritability, lethargy, stereotypy and hyperactivity in autistic children, with greater effects on younger patients (26). MIA models provide an attractive platform for further testing of such therapies.…”