2026 will shed light on whether a little-known drug helps with autism

The U.S. government made waves last year when it announced it would approve the little-known drug leucovorin for children with brain folate deficiency, a condition that appears to be linked to autism.

The decision left many doctors wary because it was based on evidence from only a few small studies. But we may soon have more information about this drug’s potential, as results from the largest trial of leucovorin for autism are expected in the first half of 2026.

Autism became a focal point of U.S. health policy in 2025 after President Donald Trump nominated Robert F. Kennedy Jr. to head the nation’s top health agencies. Kennedy, who falsely blamed rising autism rates on vaccines, pledged in April last year to identify the causes of autism by the end of September 2025.

That month, the government announced plans to approve leucovorin for people with brain folate deficiency, a condition that some research suggests 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 features of autism, such as difficulties with communication and sensory processing.

The U.S. Food and Drug Administration declined to comment on the current status of the approval process.

Leucovorin is already approved to treat certain other types of vitamin B9 deficiencies, as well as side effects of certain cancer medications. A handful of small trials have also suggested it may alleviate some difficulties faced by autistic people.

For example, a 2016 study used two daily doses of leucovorin to treat 23 autistic children with language impairments. After 12 weeks, 65 percent of them saw clinically significant improvement in verbal communication, compared to only about a quarter of the 25 children who received a placebo.

“While promising, it is important to note that leucovorin is not a cure for ASD. [autism spectrum disorder] and may only lead to improvements in speech deficits for a subset of children with ASD,” the U.S. Department of Health and Human Services said in a statement released after the announcement.

So far, studies have only tested the drug on a few dozen autistic children. Researchers have therefore expressed skepticism about the US government’s decision to approve its use. “The current evidence is very limited and very inconsistent,” says Alycia Halladay of the Autism Science Foundation in New York.

Richard Frye of Rossignol Medical Center in Arizona and colleagues are currently testing leucovorin in 80 autistic children aged 2.5 to 5 years. This trial represents a considerable size, and although some researchers have reservations that it is not large enough, it should provide a clearer picture.

About half of the children will receive the drug for 12 weeks, while the others will receive a placebo. Then, all participants will take leucovorin for an additional 12 weeks to provide additional safety data.

Researchers primarily look for changes in social communication, as reported by parents via a standard questionnaire. They will also track other signs of autism, such as irritability, hyperactivity, repetitive behaviors, sensory sensitivities and restricted interests.

Not only could this trial improve our understanding of leucovorin’s effectiveness in children with autism, but it could also answer lingering questions about the drug’s safety.

Although leucovorin is widely considered safe, little is known about its side effects particularly in autism. “The number of families who participated in these [past] the studies have not been sufficient to do a full safety study,” says Halladay.

In the trial, Frye and colleagues are assessing potential side effects every two weeks for the first 12 weeks, then every four weeks after that. They also collect routine blood samples to monitor any changes in blood clotting, immune response, or organ function.

Assuming that leucovorin provides benefits to children with autism, the underlying mechanism – beyond increasing vitamin B9 in the brain – will be assessed using analyzes carried out before and after the trial.

“We don’t know exactly what leucovorin does, but we think the brain makes more connections,” Frye says.

However, as to the usefulness of the trial, scientists disagree. “There is currently no treatment for the core symptoms of autism,” Frye says. “All the drugs we have are just kind of band-aids that treat the symptoms. This could be a treatment that not only improves the symptoms of these children, but also addresses some of the underlying mechanisms,” he says.

Halladay, on the other hand, worries that the sample size of 80 children is still too small to draw meaningful conclusions, especially since the trial is being conducted at a single site in Arizona. “I think it’s a good step in the right direction, but I think we’ll need additional studies done by more people at other sites,” she says.