The BRAIN Foundation
Synchrony Symposium 2021 Highlights
Synchrony 2021 was a live online event, held on the December 11-12. Researchers, physicians and other decision makers shared their latest research and ideas.
RESEARCH TALKS spanned a wide range of subjects, from mitochondrial research in ASD to gene-microbiome interactions and the role of zonlin in gut permeability in a mouse model of autism.
INDUSTRY TALKS featured commercial companies that are in the process of developing novel therapies and treatments with a potential for FDA approval for core or comorbid symptoms of autism. Several key players brought to the table foreseeable treatment options at various stages of FDA clinical trials and approval.
Synchrony 2021 Research Talks
Richard E Frye MD, PhD, Neurologist, Phoenix Children’s Hospital and University of Arizona College of Medicine-Phoenix: Update on Mitochondrial Research
Presentation outline, by Richard Frye, MD:
“The Brain Foundation has graciously funded three ongoing projects on mitochondrial function at our center. The first project, a double-blind placebo-controlled crossover trial of a supplement to support mitochondrial function in children with autism spectrum disorder (ASD) who have mitochondrial dysfunction is ongoing but the results are still blinded. So far major findings include the fact that children with ASD have a difficult time ingesting anything that is greater than a small quantity, making the delivery of the powder product challenging. We are working on encapsulating the product to improve delivery to a wide number of children.
The second project examines the effect of treatments on a fibroblast model of mitochondrial dysfunction in ASD. We have found unique changes in mitochondrial function in fibroblasts from children with ASD and modulatory effects of N-Acetyl-Cysteine, Rapamycin and Metformin. The third project involves examining fresh brain in children with and without ASD and/or epilepsy. Unique types of mitochondrial dysfunction are found in different types of epilepsy foci and these changes in mitochondrial function correlate with gene expression data from these regions.
Ongoing studies will correlate mitochondrial function with high-frequency oscillations and examine mitochondrial and gene expression differences between those with and without ASD.”
Edward Quadros, PhD, Professor, Department of Cell Biology, SUNY Downstate Health Sciences University: Folates, Folate Receptor Autoantibodies and the Connection to ASD
Another area of research actively being pursued in Dr. Quadros’ laboratory is the association of folate receptor autoimmunity with neural tube defect pregnancy and cerebral folate deficiency. Current research is focused on fetal and neonatal brain development and the role of folate and B12 in this process.
Dr. Quadros has established a strong link between an autoimmune disorder that produces autoantibodies against the folate receptor alpha, a membrane receptor involved in folate transport to the fetus and to the brain. Extensive research in Dr. Quadros’ laboratory is aimed at understanding the cause and effects of this autoimmune disorder and how best to prevent and treat the pathologic consequences.
Dr. Quadros holds a BSc in Chemistry from the University of Poona, a MSc in Applied Biology from the University of Bombay and a PhD in Biochemistry from the University of London.
Harris Huberman, MD, Professor of Pediatrics, The Children’s Hospital at SUNY Downstate: Folate Autoantibody Trajectories & ASD Identification in Early Childhood
Dr. Huberman currently directs the Behavior and Development rotation for Downstate’s pediatric residents and with his team runs a Child Development clinic which is heavily focused on identifying and caring for children on the Autism Spectrum.
T. Atilla Ceranoglu, MD, Director, Psychiatry Service, Shriners Hospital for Children, Massachusetts Gen. Hospital, Boston, MA: Evaluation of Transcranial Photobiomodulation in Autism Spectrum Disorder: Double-Blind, Placebo-Controlled, Randomized Clinical Study of a Novel Approach
Karen Parker, PhD, Associate Professor of Psychiatry and Behavioral Sciences, Stanford University: Vasopressin: A promising Neurochemical Marker and Therapeutic for Autism
Randy Blakely, PhD, Executive Director, Stiles-Nicholson Brain Institute and Florida Atlantic University College of Medicine: Bidirectional Neuroinflammatory and Serotonin Signaling – Basic and Translational Perspectives
Aurelio Galli, PhD, DSc, Director for Gastrointestinal Biology Research,
University of Alabama at Birmingham: Watch Flies Teaching Us Mechanisms of Neuropsychiatric Disorders
Harumi Jyonouchi, MD, Allergy and Immunology, Saint Peter’s University Hospital: Biomarkers of Innate Immune Memory in Autism Spectrum Disorders
Aim 1 Determine the state of innate immune memory (IIM) in the ASD subjects with the use of peripheral blood monocytes (PBMCs).
In initial screening of histone modification markers in purified PBMCs, we found the most significant changes in expression of H3K27ac. Unlike animal models of IIM, H3K27ac tended to be up-regulated in ASD PBMCs at high frequency. We are in the process of conducting super-enhancer CHIP sequencing using H3K27ac as a target molecule in the 1st 12 samples that include ASD subjects with or without up-regulated H3K27ac. These results will be correlated with functional assay results of monocytes.
Aim 2 Determine the feasibility of circulatory 7 miRNAs selected as the biomarkers of neuroinflammation. Seven circulating miRNAs selected based on our previous study were measured by qRT-PCR in 200 samples from both ASD and non-ASD subjects. In ASD subjects with sleep/seizure disorders had low circulatory levels of the miRNAs and did not reveal close associations with monocyte cytokine profiles. In contrast, ASD subjects without sleep/seizure disorders tended to have higher levels of these miRNA with negative associations with monocyte cytokine production.
Sarkis Mazmanian, PhD, Luis B. and Nelly Soux Professor of Microbiology, California Institute of Technology: Gene-Microbiome Interactions in an ASD Mouse Model
Joseph Buxbaum, PhD, Professor of Psychiatry, Neuroscience, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai: Connecting Rare Genetic Mutations in ASD to Common Biological Pathways
Dr. Buxbaum is a founder and communicating Principal Investigator of the Autism Sequencing Consortium, currently analyzing whole exome sequencing from 50,000 individuals to identify ASD genes. In addition, his lab has numerous human stem cell lines ongoing and has characterized more than a dozen rodent models for ASD and associated disorders. Dr. Buxbaum received his BSc in Math and Biology from Touro College, and his MSc and PhD in Neurobiology from the Weizmann Institute of Science in Israel. Dr. Buxbaum completed a Postdoctoral Fellowship in Molecular and Cellular Neuroscience at the Rockefeller University and was elected to the National Academy of Medicine in 2015.
Lipton’s group also characterized HIV-related pathways to neuronal damage, discovered the NR3 family of modulatory NMDA-type glutamate receptor subunits in the brain, characterized the molecular pathways for protecting neurons with Erythropoietin, & discovered the transcription factor MEF2C. His group showed that MEF2C activity is regulated by S-nitrosylation & serves as a master switch for neurogenesis from human neural stem cells. Dysregulated MEF2C is involved in the pathogenesis of Parkinson’s disease, Alzheimer’s disease, Autism-Spectrum Disorder, and Vascular dementia.
Ongoing research in the lab is focused on 2D human induced pluripotent stem cell (hiPSC)-derived cultures and 3D cerebral organoid models of neurodegenerative and neurodevelopmental disease and aberrant redox/S-nitrosylation pathways leading to synaptic damage.
Using these approaches, the Lipton group is developing novel drugs to combat Alzheimer’s disease, Parkinson’s disease, Vascular dementia (VaD), and other neurodegenerative disorders, as well as Autism-Spectrum Disorder and Intellectual and Developmental Disabilities. Tissue culture models complement whole-animal approaches. A plethora of techniques is employed, including chemical biology, molecular biology, patch-clamp electrophysiology, calcium imaging, and neurobehavioral paradigms.
Kazue Takahashi, PhD, Assistant Professor, Department of Radiology, Gordon Center for Medical Imaging, Harvard Medical School: Mannose Binding lectin in Health and Diseases
Paul Ashwood, PhD, Professor, Department of Medical Microbiology and Immunology, University of California, Davis: Gastrointestinal Immune Dysfunction in Autism
His current studies are at the forefront of a rapidly evolving field of investigation into the role that immune response plays in neurodevelopmental conditions such as autism. He was the first to demonstrate links between immune dysfunction and the severity of impairments that are hallmark features of autism such as social interactions and communication.
Overall, Dr. Ashwood has worked across traditional disciplinary boundaries to examine connections between different biological systems during development in order to understand how they lead to the characteristic features of autism. Specifically, he has highlighted the importance of innate immune pathways, gut-immune-brain connections and the presence of autoimmunity in some children with autism. He is author of over 100 articles on autism and has received recognition for his innovative work.
Arthur Krigsman, MD, Pediatric Gastroenterologist, Private Practice New York, and Steve Walker, PhD, Professor, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine: Improvement in Gastrointestinal Symptoms, Cognition and Behavior upon Treatment of ASD-Associated Enterocolitis
Stephen Walker, PhD, is a Professor of Regenerative Medicine at the Wake Forest School of Medicine, Winston- Salem, NC. He received his PhD in Genetics and Developmental Biology and was a Post-Doctoral Fellow in the Molecular Genetics Program at Wake Forest School of Medicine prior to joining the Department of Pediatrics faculty in the Section on Medical Genetics. One focus of his laboratory is the application of integrated multi-omics approaches and clinical data to understand the molecular basis for chronic gastrointestinal symptoms in children with an ASD diagnosis, and to understand how chronic GI problems early in childhood may impact neurodevelopment.
Alessio Fasano, MD PhD, Center for Celiac Research and Treatment; Director, Mucosal Immunology and Biology Research Center & Marcy Kingsbury, PhD, Assistant Professor of Pediatrics, Massachusetts General Hospital/Harvard Medical School: Using a Humanized Mouse Model And Human Intestinal Tissue to Evaluate the Zonulin Pathway For Personalized Treatment of ASD
Robert K. Naviaux, MD, PhD, Professor of Genetics, Biochemical Genetics and Metabolism, Departments of Medicine, Pediatrics, and Pathology Co-director, The Mitochondrial and Metabolic Disease Center (MMDC) UCSD School of Medicine: Emerging Therapeutics for ASD—Shifting Paradigms and Improving Outcomes with Mitochondrial Cell Danger Response (CDR) and Healing Cycle Research
Synchrony 2021 Industry Talks
Neil Littman, Founder and CEO, Bioverge Inc.: Democratizing Access to Early-stage Healthcare Investments
Previously, Neil was Vice President of Business Development at Notable Labs, an oncology startup and Bioverge portfolio company, where he led the development of global corporate partnerships and contributed to the strategic vision of Notable as part of the Senior Leadership Team. Neil oversaw business development at Notable through the successful completion of the company’s $40 million Series B. Previously, Neil was a member of the Executive Leadership Team and Director of Business Development at the California Institute for Regenerative Medicine.
Prior to CIRM, Neil was a healthcare investment banker at Thomas Weisel Partners and Deutsche Bank and worked on transactions totaling over $1 billion. His primary focus was on strategic advisory and public and private financings. Neil received a Master of Science in Biotechnology from The Johns Hopkins University.
Bioverge is an investment platform and syndicate that connects individual investors with highly curated investment opportunities at the intersection of health + tech (or TechBio): “We help our members invest in the health-related causes they care about most and we help companies bridge the valley of death. At Bioverge, we believe we can all do well by doing good.”
John Slattery, Co-founder, President, and CEO, BioROSA: Metabolic Autism Prediction (MAP) Study: A multicenter prospective double-blind case/control study assessing metabolic prediction of ASD from a developmental pediatrics waitlist
John has extensive ties to the autism clinical, research, and patient community and a wide knowledge base of ASD from a clinical, scientific, and business perspective. At ACH John was the personnel manager for the autism program and managed a team of 10 and was the director of autism translational research under Dr. Richard Frye, MD/PhD. John joined a software startup company in 2017 where he was in charge of sales and R&D. Prior to that he worked at UPenn doing brain imaging research from 2007-2010. John has a BA from the University of Arkansas and has multiple certifications in clinical research.
In this talk John Slatter gave an update on their ongoing clinical trial for metabolic prediction of autism using BioROSA developed laboratory methods
Stephen O’Quinn, PharmD, Vice President, Medical Affairs, Zynerba Pharmaceuticals: ZYN002 Cannabidiol Transdermal Gel Efficacy and Safety – Recent Clinical Research Advances in the Treatment of Autism and Fragile X Syndrome
Eugene Prahin, CFO, Yamo Pharmaceuticals: L1-79 for Treatment of Core Symptoms of Autism
Colleen Kraft, MD, MBA, FAAP, Senior Medical Director, Clinical Adoption, Cognoa and Professor of Pediatrics, Keck School of Medicine, University of Southern California: Streamlining the Current Autism Diagnostic Pathway
C.E.O., Sirica Therapeutics: Sirica Therapeutics – Making Therapy Fun!
We are building a therapeutic device by putting together a combination of technologies namely, robotics, virtual reality and machine learning that can solve some of the biggest challenges faced by this population. This device will use physical, mental and psychological tools to help create a program to calm behaviors, improve achievement and enhance neuroplasticity. Several thousand data points will be collected automatically and are stored in the cloud. Machine learning algorithms can make changes to the program very quickly. It can generate automatic progress reports. A therapist could run a few machines simultaneously while in the clinic or even remotely from a patient’s home. It will be designed to be an adjunct to the one on one therapy.
Stewart Campbell, Ph.D., CEO Axial Biotherapeutics: Targeting bacterial metabolites as a strategy to manage irritability associated with autism
James N. Woody, MD PhD, CEO, MARAbiosystems: MaraBio, a Precision Medicine ASD diagnostic Company
Erik Won, President & Chief Medical Officer, Wave Neuroscience: Biometric-Guided TMS for Kleefstra Syndrome
Her current research and clinical interests include Autism, Language Delays, Developmental Delays, Cognition, and neurological and psychological response to trauma.
During the last two years, as a CSO of Jelikalite, she has been working on developing and validating tPBM technology for treating Autism in young children.