A study published on Thursday (27) in the journal Science describes how genetic mutations linked to severe forms of autism change the way proteins interact inside cells of the developing brain. The work, led by researchers at the University of California, San Francisco (UCSF), produced what its authors present as the largest molecular map of autism ever built and opens the way to testing drugs for the condition, according to reports by Folha de S.Paulo, in partnership with The New York Times, and by the trade publication Genetic Engineering and Biotechnology News (GEN).

The team, led by UCSF's Quantitative Biosciences Institute (QBI) and its psychiatry department, mapped the proteins encoded by 100 genes associated with autism and identified more than 1,800 interactions among them, 87% of which had never been described before. The researchers also analyzed 54 mutations found in patients and combined that data with structural models from AlphaFold and experiments in human brain organoids, small lab-grown clusters of brain cells, and in embryos of Xenopus, a frog used in research. That allowed them to pinpoint exactly where each mutation breaks the connections between proteins.

The study's central finding is convergence: mutations in different genes can disrupt the same protein complex. In one example cited in the paper, mutations in the FOXP1 and FOXP2 genes disturb the same interaction between the FOXP1 and FOXP4 proteins, which speeds up the maturation of cortical neurons and raises the excitability of neural circuits in the organoids. The practical implication is that, in the future, a single drug might treat several genetically distinct forms of autism, instead of requiring a different therapy for each mutation.

The result matters most for what specialists call profound autism. In about 30% of people with autism, those with the most severe disabilities, scientists have already identified rare single-gene mutations that are probably associated with the disorder. "This study maps the exact molecular machinery that is altered, including the specific protein interactions, down to the interfaces we can target with a drug," Nevan Krogan, director of QBI and a senior investigator at the Gladstone Institutes, told GEN. Matthew State, chair of UCSF's psychiatry department and a senior author of the study, said the work "opens up a whole new world of possibilities for therapeutic targets".

What is confirmed and what remains hypothesis

The two levels should be kept apart. What the study firmly delivers is the map itself: the protein interactions and the exact points where mutations break them, observed in the laboratory. What remains preliminary is the therapeutic promise. No drug has been tested in patients based on these results, and lab-grown organoids reproduce only part of how a real brain works. Dan Geschwind, a UCLA neurogeneticist who did not take part in the work, summed up the current stage to Folha: "This amounts to mapping uncharted territory, which is really necessary to move biology forward."

For families in Brazil and elsewhere, the practical advice does not change. The care available today is still early diagnosis and interventions backed by scientific evidence, such as behavioral, speech and occupational therapy, along with regular follow-up. Findings like these point to a promising research path, reinforced by a US$ 46 million grant that QBI received from the Aligning Research to Impact Autism (ARIA) initiative to turn the map into drug candidate molecules, but any concrete treatment is still years away. Until then, caution also applies to unproven therapies that promise a cure for autism: no approved drug today treats the genetic causes of the condition.