FDA Approves Leucovorin for Rare Brain Disorder, but Not Autism

• Federal regulators have approved leucovorin for the treatment of cerebral folate deficiency, a rare neurological disorder.
• The FDA approval, however, did not include the use of leucovorin as a treatment for autism.
• The Trump administration has touted leucovorin as an autism treatment, but experts agree that more research is needed before leucovorin should be approved for this purpose.

A medication used primarily to help relieve the side effects of chemotherapy has been given the green light to be used as a treatment for a rare neurological disorder.

Officials at the Food and Drug Administration (FDA) announced on March 10 the approval of the drug leucovorin to help treat adults and children with cerebral folate deficiency. This rare condition is characterized by low levels of vitamin B9 in the brain.

However, the FDA announcement did not mention the use of leucovorin as a potential treatment for autism.

In September 2025, President Donald Trump and other administration officials suggested that the FDA had started a process to approve leucovorin as a treatment to manage symptoms in autistic people. However, there’s no word yet on a timetable or process for such an approval.

Leucovorin is the first approved treatment for cerebral folate deficiency. The FDA decision is being praised as long overdue relief for individuals with that condition.

“Today’s approval represents a significant milestone for patients living with cerebral folate transport deficiency due to the FOLR1 variant, a rare genetic condition that has had no FDA-approved treatment options until today,” said FDA commissioner Marty Makary, MD, in the agency’s announcement.

Leucovorin is a prescription medication used mainly to reduce the toxic side effects of chemotherapy agents such as methotrexate.

The medication works by helping to restore folic acid to healthy cells that have had that substance depleted by the effects of chemotherapy.

Leucovorin is considered to be effective as a “rescue agent” for people undergoing certain types of chemotherapy.

• developmental delays
• seizures
• movement abnormalities

It’s estimated that 1 in 1 million people worldwide have cerebral folate deficiency, although the true prevalence is unknown. It’s also been estimated that 38–70% of autistic children may have cerebral folate deficiency.

However, experts say those percentages may be inflated because much of the data has been drawn from FRAT tests, a blood exam that can be inaccurate.

While individuals with cerebral folate deficiency may have a higher risk of autism, but autistic people don’t necessarily have a higher risk of cerebral folate deficiency.

Alycia Halladay, MD, the chief science officer for the Autism Science Foundation, said she’s glad that people with cerebral folate deficiency finally have a treatment.

“This will probably help them. The mechanism is there,” she told Healthline. “I feel any relief would be helpful.”

Antonio Hardan, MD, a professor of psychiatry and behavioral sciences at Stanford University, said that early intervention with leucovorin for cerebral folate deficiency is key.

“Case reports [support] complete clinical and radiological recovery when treatment is provided before the age of 2 years,” Hardan told Healthline.

While early intervention in autism is also crucial, it’s too soon to recommend leucovorin as a treatment.

Halladay expressed relief that leucovorin wasn’t approved as an autism treatment because there isn’t yet a scientific justification for this particular use.

“I’m glad the FDA used a scientific approach and used rigor to make this decision,” she said.

Hardan echoed this sentiment. “There is some evidence from small randomized controlled trials supporting the use of leucovorin for the treatment of autism. However, these studies have several design limitations, including small sample sizes and non-rigorous inclusion/exclusion criteria,” he said.

In September, President Trump said the approval of leucovorin as an autism treatment would give “hope to the many parents with autistic children that it may be possible to improve their lives.”

Makary echoed that sentiment, estimating that “hundreds of thousands of kids, in my opinion, will benefit” from the approval of leucovorin.

After that press briefing, officials at the Health and Human Services (HHS) Department clarified those comments, saying that leucovorin “is not a cure” for autism and “may only lead to improvements in speech-related deficits for a subset of children.”

The research on leucovorin and autism has mostly consisted of small studies with fewer than 100 participants, many done repeatedly by the same researchers.

The results of one of the studies, published in the European Journal of Pediatrics, were retracted in January after the authors identified several errors in their data.

There has been some anecdotal evidence that leucovorin can provide some benefits to communication and behavior for some autistic children, specifically those with cerebral folate deficiency or evidence of folate metabolic differences.

According to the American Academy of Pediatrics (AAP), however, more research in this area is still needed.

“The evidence for leucovorin and use for autism is currently limited,” the AAP said in an FAQ sheet about leucovorin use in autism and cerebral folate deficiency.

“Small studies show benefits to communication and behavior for some autistic children, specifically those with CFD or evidence of folate metabolic differences. Larger independent trials are warranted to better understand which patients may benefit. More evidence on efficacy and safety is needed before pediatricians can broadly recommend leucovorin,” the AAP said.

The Autism Science Foundation agreed, saying more studies are needed before leucovorin can be considered as a treatment for autism.

Halladay said that large-scale studies that examine safety and efficacy need to be completed before leucovorin can be considered as an autism treatment.

An HHS official appeared to agree, telling NBC News this week that there is not enough data to support leucovorin’s use as an autism treatment.

“We don’t have sufficient data to say that we could establish efficacy for autism more broadly,” the official said. “It’ll be up to patients to talk with their physicians to see if that might be right for them.”

Doctors can prescribe leucovorin as an off-label treatment for autistic children. Some have apparently been doing so.

A recent report published in The Lancet stated that leucovorin prescriptions for children rose 71% during the 2 months following President Trump’s announcement in September.

Halladay expressed concern about that increase, as well as the fact that people can go online and purchase folate acid products with vitamin B9 that are similar to leucovorin.

“All this can lead to false hope from companies that prey on families who will do anything to help their child,” she said.

Halladay encouraged families of autistic children to listen to medical professionals over what they read in the media.

“Talk to your doctor. Listen to your doctor and don’t listen to the internet,” she said.