About this Project

About one-third of children with autism spectrum disorder (ASD) demonstrate a major neurodevelopmental regression (NDR) in which they loss skills, most commonly language and social interactions, as well as develop restricted and repetitive behaviors, leading to the diagnosis of ASD.

Over the past ten years we have developed a cellular model of ASD in which the mitochondria, the powerhouse of our cells, demonstrates a unique type of mitochondrial dysfunction that is quantitatively different from classically defined mitochondrial disease. This model recapitulates the clinical picture in which an environmental trigger (e.g., toxicant, inflammation, infection) results in NDR. Furthermore, we have found that children with ASD and NDR may have a distinct mitochondrial signature. The goal of this project is to further develop this model and mitochondrial biomarker of NDR as well as discover novel targeted treatments for this subset of children with ASD.

About this Project

Our group has found that a substantial subgroup of individuals with Autism spectrum disorder (ASD) have abnormalities in folate metabolism which prevents folate from being transported into the brain. This is primarily caused by the presence of the folate receptor alpha autoantibodies (FRAAs) in the blood. FRAAs block the ability of the folate receptor alpha to transport folate across the blood brain barrier. In addition, our previous clinical trials have shown that a safe, effective, well-tolerated special form of folate known as leucovorin improves core and associated symptoms by bypassing this block. Since this treatment potentially addresses the underlying pathophysiology driving ASD. it could have disease-modifying potential.

This project aims to extend our ongoing research to optimize its impact:

1. To better understand transgenerational folate pathway and associated metabolic abnormalities in ASD we plan to investigate the inheritance pattern of FRAAs and associated metabolic abnormalities by studying family members including the child with ASD, mother, father, and siblings as well as control families without children with ASD.
2. We aim to study alteration in methylation in the nuclear and mitochondrial genome by studying its association with folate pathway abnormalities and mitochondrial function in the families with and without children with ASD.
3. We plan to develop alternate methods with measuring FRAAs and identify the soluble folate receptor / binding protein(s) so an assay to measure them can be developed.
4. Ongoing work from our group is developing new and validating existing instruments in minimally verbal individuals so these individuals can be studied in clinical trials and treatments can be developed for them.

About this Project

Complete Onboarding: Medical Conditions, Prenatal Risks, Environment, History, Evaluations, Neurodevelopmental Milestones, Symptoms, Interventions, Variables, and Education.  This is a project with a big name and a big goal. We are creating a comprehensive approach to gathering and analyzing patient data to help diagnose ASD and other neurodevelopmental conditions, as well as track treatment outcomes over time.

The goals for this project are:

1. Ease-of-use for parents/guardians to supply necessary patient information
2. Robust reporting for clinicians to quickly and thoroughly analyze the patient's situation, standardization of data collection practices
3. Longitudinal results that track outcomes over time

We believe that this tool will help clinicians diagnose and treat ASD and other neurodevelopmental disorders.

About this Project

We are developing medical treatments that will target abnormal physiological processes underlying ASD in order to correct the underlying disturbances that may be causing ASD. In order to do this, we are investigating metabolic pathways. Many metabolic pathways are known to be abnormal in ASD but metabolism is very complex, so the metabolism disruption needs to be studied carefully to identify the key pathway or pathways that need to be targeted. The wonderful thing about metabolism is that is can be fixed with non-toxic treatments including diet and vitamins. We have already performed several research studies demonstrating the power of correcting metabolic pathways. Further studies are needed to understand these pathways better, develop biomarkers and optimize targeted treatments.

About this Project

Careful research and clinical observations have led to our discovery that folate abnormalities may play a role in the etiology of ASD. Further work led to the discovery of biomarkers for folate abnormalities and a potentially effective treatment. The treatment is a special form of folate that bypasses blocks in folate metabolism that are associated with ASD. These research and clinical observations have been preliminary validated but further research is needed to further develop this treatment for children with ASD and determine if this treatment can be used before ASD symptoms arise to prevent ASD.