Mitochondrial Dysfunction in Epilepsy and Autism
Investigating High-Frequency Oscillation as a Biomarker of Mitochondrial Dysfunction associated with Epilepsy in Autism.
Individuals with Autism Spectrum Disorder (ASD) are at an increased risk for epilepsy with the risk of new onset seizures increasing into adolescents and young adulthood. Epilepsy in individuals with ASD is more difficult to treat and is the leading cause of death in young adults with ASD. At this time we need better biomarkers of the risk for developing epilepsy in those with ASD so we can predict those that require treatment or monitoring and a better understanding of the biological mechanism that underlie epilepsy so we can develop novel effective therapies.
About This Project
Mitochondrial dysfunction has been linked to epilepsy but, at this time, biomarker of mitochondrial dysfunction in the brain are very limited to research based approaches. Our laboratory has developed the ability to measure mitochondrial function in fresh human brain surgically excited to remove areas that cause epilepsy.
We have correlated mitochondrial dysfunction in these resected areas of brain with high frequency oscillations (HFOs) from electrophysiological recordings obtained preoperatively during the epilepsy evaluation. This research will focus on studying mitochondrial dysfunction as a cause of epilepsy in individuals with and without ASD as well as the correlation with these areas of mitochondrial dysfunction with HFOs that can be recorded non-invasively as a biomarker of mitochondrial associated epilepsy.
Such research will improve the identification of epilepsy in individuals with ASD as well as identification of mitochondrial dysfunction in the brain so effective targeted treatments can be provided to control seizures.
Bioenergetic Signatures of Neurodevelopmental Regression
Associated Mitochondrial Dysfunction: Further Development of In Vitro Models and Pathways to Treatment.
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.
About This Project
Understanding Transgenerational Folate Abnormalities
In Children with Autism Spectrum Disorder and Their Families
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.
About This Project
- 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.
- 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.
- 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.
- 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.
Metabolic Treatments
Targeting Abnormal Physiological Processes Underlying ASD
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.
About This Project
Leucovorin
Using Folate Treatments to Prevent ASD
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.
About This Project
The C.O.M.P.R.E.H.E.N.S.I.V.E Project
Complete Onboarding: Medical Conditions, Prenatal Risks, Environment, History, Evaluations, Neurodevelopmental Milestones, Symptoms, Interventions, Variables, and Education
