You may not have heard of leucovorin, but the US government is championing it to combat rising rates of autism.
Hannah Bayer/Reuters
The US government caused a stir last year when it announced it would approval of a little-known drug leucovorin for children with cerebral folate deficiency, a condition that appears to be associated with autism.
The decision made many doctors wary because it was based on data from only a few small studies. But we may soon have more information about the drug's potential, with results from the largest study of leucovorin in autism expected in the first half of 2026.
Autism became the focus of U.S. health policy in 2025 after President Donald Trump appointed Robert F. Kennedy Jr. to lead the nation's top health agencies. Kennedy, who Vaccines are falsely blamed for the rise in autismpromised last April that it would identify the causes of autism by the end of September 2025.
That same month, the government announced it planned to approve leucovorin for people with cerebral folate deficiency, a condition that some studies have suggested. affects up to 40 percent of autistic people. It interferes with the absorption of vitamin B9 in the brain, leading to symptoms similar to some characteristics of autism, such as difficulties with communication and sensory processing.
The US Food and Drug Administration declined to comment on the approval process.
Leucovorin is already approved to treat some other types of vitamin B9 deficiency, as well as side effects of some cancer drugs. Several small studies have also shown that it may alleviate some of the difficulties faced by autistic people.
For example, 2016 study used two daily doses of leucovorin to treat 23 autistic children with language impairment. After 12 weeks, 65 percent of them had clinically significant improvements in verbal communication, compared with about a quarter of the 25 children who received placebo.
“While this is promising, it is important to note that leucovorin is not a cure for ASD. [autism spectrum disorder] and may only lead to improvement in language deficits in a subset of children with ASD,” the U.S. Department of Health and Human Services said in a report. statement released after announcement.
So far, the drug has only been tested on a few dozen children with autism, so researchers have expressed skepticism about the US government's decision to approve its use. “The evidence at the moment is very limited and very contradictory,” says Alicia Halladay at the Autism Science Foundation in New York.
Richard Fry at Rossignol Medical Center in Arizona and his colleagues are now testing leucovorin on 80 autistic children aged 2.5 to 5 years. The study represents a significant jump in size, and while some researchers have concerns that it is not large enough, it is expected to provide a clearer picture.
About half of the children will receive the drug for 12 weeks, while the rest will receive a placebo. All participants will then take leucovorin for an additional 12 weeks to obtain additional safety data.
Researchers are primarily looking for changes in social communication reported by parents on a standardized questionnaire. They will also monitor for other signs autismsuch as irritability, hyperactivity, repetitive behavior, sensory sensitivity and restricted interests.
Not only could this study improve our understanding of whether leucovorin helps children with autism, but it could also answer long-standing questions about the drug's safety.
Although leucovorin is widely considered safe, little is known about its side effects, especially in autism. “The number of families who took part in these [past] there were not enough studies to conduct a full safety study,” Halladay says.
In the study, Fry and colleagues assess potential side effects every two weeks for the first 12 weeks and then every four weeks. They also regularly collect blood samples to monitor any changes in blood clotting, immune response, or organ function.
Assuming that leucovorin does indeed benefit autistic children, the mechanism behind this – other than increasing vitamin B9 levels in the brain – will be assessed through scans taken before and after the study.
“We don't know exactly what leucovorin does, but we think what's happening is that the brain is getting more connections,” says Fry.
However, when it comes to how useful the research will be, scientists disagree. “There is currently no treatment for the core symptoms of autism,” says Fry. “All the drugs we have are just patches that treat the symptoms. These could be treatments that not only improve the symptoms in these children, but actually target some of the underlying mechanisms,” he says.
Halladay, on the other hand, is concerned that the sample size of 80 children is still too small to draw meaningful conclusions, especially since the study is only being conducted at one location in Arizona. “I think this is a good step in the right direction, but I think we will need more research by more people at other sites,” she says.
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