Early Treatment of Language Impairment in Young Children with Autism Spectrum Disorder with Leucovorin Calcium

Autism Spectrum Disorder (ASD) has an enormous impact on individuals, families and society, yet there is no FDA approved treatment that addresses underlying ASD pathophysiology and/or core deficits. However, a growing body of evidence indicates that leucovorin, a form of folate (vit B9) that bypasses physiological blocks in folate metabolism found in ASD, can significantly improve verbal communication as well as other symptoms associated with ASD. Our recent double blind placebo controlled (DBPC) trial published in Molecular Psychiatry, found that leucovorin significantly improved verbal communication in children with ASD with a medium-to-large effect size especially in the subset positive for the folate receptor autoantibody (FRAA+). However, the effect on social communication measures was mixed. We hypothesize that leucovorin could have a definitive positive impact on social communication if treatment is initiated beginning around 2-3 years of age, when neuroplasticity is greater and social communication is being established. We will also study the neuronal mechanisms underlying leucovorin's improvement in social communication / language. We propose a multisite 12-week DBPC trial with 12-week open-label extension of leucovorin in 2.5-5 year old children with ASD who are FRAA+. Our primary outcome will be the Brief Observation of Social Communication Change, a sensitive, validated, direct assessment of change in social communication developed by C. Lord at the Center for Autism and the Developing Brain. We will also study the neuronal mechanisms underlying leucovorins improvement in social communication / language. We propose a multisite 12-week DBPC trial with 12-week open-label extension of leucovorin in 2-5 year old children with ASD who are FRAA+.