Synchrony 2022: Catalyzing Research and Treatments to Benefit Individuals with Neurodevelopmental Disorders including Autism Spectrum Disorders

**Background:** The Synchrony 2022 conference, held December 2–4, 2022, was organized by The BRAIN Foundation (Pleasanton, CA, USA) as a translational medicine conference focused on treatments for neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD). The conference aimed to bridge basic and clinical sciences from academia and industry to expedite translation of ASD research from bench to bedside and from academic development to commercial application. The conference featured academic sessions, industry presentations, and four roundtables addressing key challenges in the field.

**Methods:** The three-day conference was divided into three primary sections: academic sessions featuring established and early-career investigators, industry sessions from companies developing ASD treatments, and four roundtables that brought together academic researchers, clinicians, industry partners, and parents of children with ASD. Research presentations were selected from submitted abstracts, with two awards of $15,000 each given for Most Innovative Research and Most Impactful Research. The invited speakers session on the final day was the most widely attended by the general public.

**Key Results:** Multiple significant findings were presented. Randy Blakely discussed research on mice expressing a hyper-functional ASD-associated variant in the serotonin transporter (SERT Ala56), demonstrating hyperserotonemia and behavioral traits including changes in social communication and repetitive behavior. Naveen Nagarajan found that loss of function in the microglia Hoxb8 gene leads to repetitive grooming behaviors and chronic anxiety through cortico-striatal circuit defects. Stephen Smith identified the SRC-family kinase FYN as the most dysregulated network node in FMR1 mutant mice, with inhibition of SRC-family kinases normalizing molecular and behavioral phenotypes. Brittany Needham reported that the gut microbial metabolite 4-ethylphenyl sulfate (4EPS) was found at high levels in ASD mouse models and impaired oligodendrocyte maturation and myelination, associated with anxiety-like behaviors. Richard Frye reported that mitochondrial disease is found at high rates (~5%) in those with ASD, with some children showing higher respiration rates and reserve capacity linked to prenatal air pollution and nutritional metal exposure. T. Atilla Ceranoglu reported that transcranial photobiomodulation (tPBM) resulted in a 25% decrease in SRS-2 scores and CGI-I scores, with several patients showing a 10-point increase in GAF scores. John Gaitanis reported that using pure CBD and THC in certain dosages had a 49% improvement rate in overall behavior in ASD. Alessio Fasano found overrepresentation of HP2-2 and underrepresentation of HP1-1 in ASD patients with gastrointestinal symptoms. Richard Boles studied 20 patients with trio whole genome sequencing, finding 15 cases with monogenic causal diagnoses and 16 cases with treatment recommendations based on DNA sequencing results. Joseph Buxbaum reported that 350 genes have been found to have mutations that can lead to ASD, with functional signatures identified for 77 main ASD risk genes using CRISPRi.

**Clinical Implications:** The conference identified several promising therapeutic approaches and diagnostic tools. Microbiota transplant therapy showed improvement in ASD symptoms and significant reduction in gastrointestinal symptoms for Pitt-Hopkins syndrome. Levoleucovorin treatment for children with ASD and verbal communication impairment resulted in significant improvements in verbal communication in a double-blind placebo-controlled study. The conference established four working groups to develop consensus papers and clinical guidelines on neuroinflammation, FDA approval pathways, biomarkers for ASD diagnosis and treatment, and epilepsy management in ASD. The BRAIN Foundation reported funding over $1M in research in the past year. The conference highlighted that ASD research remains deeply underfunded compared to other neurological disorders, with calls for coordinated efforts to influence NIH research priorities.