A novel approach to treating autism spectrum disorder (ASD), Alzheimer’s disease, and even aggressive brain cancers is gaining momentum thanks to groundbreaking research led by Haitham Amal, an associate professor at Hebrew University and visiting professor at Harvard Medical School. His work, centered on controlling nitric oxide levels in the brain, has already secured FDA orphan drug designation for Phelan-McDermid syndrome (PMS), a subtype of autism, and is poised to enter Phase 1 clinical trials as early as 2026.
The Rising Prevalence of Autism and the Nitric Oxide Link
According to 2022 data, approximately 1 in 31 children now exhibit signs of autism spectrum disorder—a significant increase since 2000. Amal’s research, originating from his postdoctoral work at MIT in 2015, has identified an abnormal production of nitric oxide in the brains of individuals with ASD. This finding, initially published in Molecular Psychiatry, was later confirmed to have a causal effect, driving the development of a new class of small-molecule drugs.
The core mechanism involves selective inhibition of neuronal nitric oxide synthase. This aims to reduce excessive nitric oxide production resulting from genetic mutations, thereby reversing neuronal and behavioral deficits observed in autism. Unlike existing symptom-management drugs like risperidone, which carry substantial side effects, this approach directly addresses the underlying pathological mechanisms.
Beyond Autism: Targeting Cancer and Alzheimer’s
Amal’s company, NeuroNOS, is developing a dual-action drug targeting glioblastoma, a deadly brain cancer. The mechanism extends beyond simply inhibiting nitric oxide; it also damages tumor DNA. The link between nitric oxide and cancer stems from genetic mutations that trigger calcium overproduction, further activating nitric oxide synthase.
The same small-molecule approach is being adapted for Alzheimer’s disease and frontal temporal dementia, with the aim of filing for orphan drug status in the near future. The potential for accelerated approval through the FDA’s orphan drug program provides a streamlined path for these therapies.
Environmental Factors and Early Diagnosis
Recent research highlights a critical link between air pollution and increased ASD risk. Amal’s team found that exposure to fine particulate matter (PM2.5), including nitric oxide, induces autism-like phenotypes in human organoids. This discovery has secured a $17 million grant from the California Institute for Regenerative Medicine to further investigate the role of environmental factors in neurodevelopmental disorders.
Additionally, in collaboration with Point6 Bio, Amal’s lab is developing a simple blood test for early autism diagnosis, potentially revolutionizing detection and intervention strategies. This diagnostic tool is considered by Amal to be as important, if not more so, than any potential Nobel Prize.
Administration and Development Timeline
The ASD drug will be administered as a powder added to foods or drinks, following successful dose-range studies in dogs and rats. The glioblastoma drug is further behind in development but shows promising preclinical results.
“Developing a drug and biological diagnostics for autism is even more important to me, on a personal level, than a Nobel Prize,” says Amal. “I think [our small-molecule drug] gives hope to millions of families and kids.”
The convergence of scientific breakthroughs, expedited regulatory pathways, and targeted therapies positions Amal’s work as a pivotal moment in the fight against neurological and developmental disorders. The long-term impact of these advancements remains to be seen, but the initial findings offer a clear path towards more effective treatments and earlier diagnoses.
