The Effect of Cancer Treatments on Macrocephaly due to Autism

Abstract

By Molly Macleod, Biochemistry

Advisor: Edward Merino

Presentation ID: PM_D15

Abstract: Autism Spectrum Disorder (ASD) is defined by both restrictive, repetitive actions and communication deficits. It affects 1 in 59 people across all races and socioeconomic groups. Comorbidities include sleep disorders, intestinal disorders, and seizures. A subset of ASD patients have a mutation in the tumor suppressor gene phosphatase and tensin homolog (PTEN). This mutation and PTEN-associated autism can manifest in a variety of phenotypes. One striking phenotype seen in both patients and disease specific animal models is macrocephaly. PTEN is the main negative regulator of the phosphoinositide 3-kinase (PI3K) pathway and has been well described in cancer research. The overall goal of this project is to assess if a treatment shown to be successful in PTEN-deficient cancer can rescue phenotypes associated with PTEN-deficient ASD. Specifically, it is known that inhibition of one specific PI3K isoform, p110_, inhibits tumor growth in cancers with a driving mutation in PTEN. Inhibition of other isoforms yield no change in tumorigenesis. In this study, we assessed if macrocephaly phenotypes in a neuron-specific PTEN deficient mouse model can be decreased by a p110_ specific inhibitor, GSK6A. Macrocephaly was quantified through histological staining and measurement of the hippocampus in vehicle- or GSK6A-treated PTEN knockout mice and unaffected littermate controls. This research allows for a better understanding of p110_ inhibitors as potential treatment for PTEN-associated ASD.