Treatment trial to measure biochemical markers of oxidative stress and mitochondrial dysfunction, to demonstrate that they are improved with the treatment and they correlate with improvements in core symptoms of autism and behavior.
This is a proposal requesting funding for a 50-subject double-blind placebo controlled clinical trial focusing on treating children with autism and mitochondrial dysfunction with a treatment that targets improving mitochondrial function. NeuroNeeds (https://www.neuroneeds.com/), which produces a high quality supplement that targets the mitochondria, has offered to donate the supplement and the placebo. The trial would measure biochemical markers of oxidative stress and mitochondrial dysfunction to demonstrate that they are improved with the treatment and they correlate with improvements in core symptoms of autism and behavior, which will also be measured.
The goal of this study is to demonstrate that core symptoms of autism spectrum disorder (ASD) can be improved by targeting an important metabolic system involved in the function of every cell in the body called the mitochondria. This study will validate a novel approach to treating ASD, thereby expanding the treatment options for children with ASD. We will evaluate the effectiveness of a wide-spectrum metabolic supplement to improve core ASD symptoms through normalizing metabolic function, in particular, mitochondrial function. Patient entering the trial will have known mitochondrial dysfunction as the treatment target. As we believe that about 50% of children with ASD have some form of primary or secondary mitochondrial dysfunction; we will target these children. We hypothesize that a wide range of ASD symptoms will improve because mitochondria is central for normal cellular physiology throughout the body, thus implying that improving mitochondrial function will have wide ranging positive effects on many body systems that are known to be abnormal in ASD including the brain, gastrointestinal system and immune system.
Studies to quantify symptom improvement and behavioral/cognitive changes in ASD children following treatment for their chronic GI inflammation.
An inflammatory bowel disease (IBD) phenotype co-occurs frequently in children with autism spectrum disorder (ASD) having chronic gastrointestinal (GI) symptoms. Ileo-colitis (inflammation of ileum and colon) is a prominent finding in ASD GI symptomatic children undergoing diagnostic ileo- colonoscopy, and, in our clinical experience, is related, perhaps, to the GI symptoms. The negative impact of untreated gastrointestinal symptoms affect behavior, sleep, and severity of core ASD features. These clinical observations have never been systematically evaluated, documented, analyzed, and reported. The studies proposed herein will, for the first time, quantify symptom improvement and behavioral/cognitive changes in ASD children following treatment for their chronic GI inflammation.
The goal of this series of studies is to obtain data that would be exceptionally beneficial in generating a more uniform “standard of care” for children with ASD being evaluated for chronic gastrointestinal symptoms. The studies will not only quantify symptom improvement and behavioral/cognitive changes in ASD children following treatment, but in addition, the pre- and post- treatment testing will provide the means to validate our finding of a blood-based biomarker for the ASD phenotype and a molecular metric to measure efficacy of treatment.
Study to address the basic question of how inflammation can contribute to GI co-morbid features and severity of behaviors in ASD children, and also open new cell specific therapeutic approaches for ASD based on the manipulation of immune cells. (Supplemental Grant)
Gastrointestinal problems are a major issue in over half of all individuals with ASD. Untreated GI problems are now thought to impact many behavioral symptoms associated with ASD including aggression, sudden irritability, unexplained crying, anxiety, sleep disorders, social withdrawal, self-injury and hyperactivity. Children with ASD and GI co-morbidities tend to score far worse on behavior assessments suggesting that these chronic GI symptoms intensify core ASD deficits. Undoubtedly, GI problems in ASD impact the child’s and family’s quality of life. Yet, very few children with ASD and GI comorbidity are treated for their GI symptoms. There is a large gap in our knowledge regarding why children with ASD are 6-8 times more likely to have GI issues. Our previous work has highlighted that increased immune activation occurs in the GI tract. More immune cells are activated and more of these cells travel into the gut lining, leading to inflammation. Regulation of inflammation and control immune responses is also decreased.
The results of this study will not only address the basic question of how inflammation can contribute to GI co-morbid features and severity of behaviors in ASD children, but may also open new cell specific therapeutic approaches for ASD based on the manipulation of immune cells.
In the GI tract, we propose to study immune cells that are supposed to help calm inflammation that could occur in response to bacteria or food in the gut, such as Treg cells. Our proposed work will look at these cells specifically and answer the questions: Do these cells work properly? What do they produce? How many are there? Can they be formed correctly? If they
appear, are they stable? Do they respond to signals from the body to be better regulators or switch to a cell type that is harmful? By answering these fundamental questions we hope to learn a great deal about the biology of these cells in young children with ASD and GI co-morbid features. We believe that there will be overlap between the faulty function of immune cells and severity of GI symptoms and behavioral symptoms.