By Julie Steenhuysen
CHICAGO (Reuters) -U.S. President Donald Trump’s embrace of an old generic drug called leucovorin for use against a rare disorder that causes autism-like symptoms has triggered a surge in demand from parents who believe it could unlock speech and social connection in their autistic children.
That has become a challenge for pediatricians and specialists who caution the science on leucovorin in people with autism is limited and does not support widespread use.
In the month since Food and Drug Administration Commissioner Marty Makary promoted the decades-old drug from GSK, saying it could help “hundreds of thousands” of children with autism, doctors and researchers say they have been inundated by parents seeking information.
“My Facebook feed is flooded with parents swearing that leucovorin works,” said Dr. David Mandell, a professor of psychiatry and autism researcher at the University of Pennsylvania.
LACK OF DATA
Tens of thousands of people have joined a Facebook group called Leucovorin for Autism started in May by Keith Joyce, legal guardian to four-year-old Jose, who is taking the drug.
Joyce credits Jose’s improvements in verbal communication and social awareness to leucovorin. The site gained 5,000 members on the day of Trump and Makary’s White House announcement and now has 84,000.
Mandell and other scientists and doctors say FDA’s endorsement without requiring large, randomized clinical trials leaves practitioners facing emotional pleas from families while lacking data, guidance or confidence to prescribe the drug responsibly.
Leucovorin is approved to treat chemotherapy side effects but can be prescribed off-label for autism symptoms.
“It puts physicians in a very tough position because they’re being asked to prescribe something that is not evidence-based,” said Dr. Shafali Jeste, an autism expert and head of pediatrics at UCLA, who does not prescribe leucovorin despite repeated requests.
On Friday, the American Academy of Pediatrics said it does not recommend leucovorin for routine use in children with autism.
Autism rates have risen to 1 in 31 8-year-olds, the U.S. Centers for Disease Control and Prevention reported in April. Finding the condition’s root cause and potential treatments is something Health Secretary Robert F. Kennedy Jr. and Trump have championed.
RARE NEUROLOGICAL CONDITION
Despite the FDA commissioner’s broad comments, his agency proposed a narrower expanded approval tied to cerebral folate deficiency (CFD), a genetic condition that can cause autism-like symptoms. It affects roughly one in 1 million children worldwide.
The argument for wider use is built on small studies suggesting many children with autism have autoantibodies that block folate – a vitamin important for brain signaling – from entering the brain, causing a deficiency similar to CFD.
An estimated 75% of autistic children are believed to have these autoantibodies, but their significance is unproven, said Dr. Karam Radwan, director of the Neurodevelopmental Disorders Program at the University of Chicago.
A Health and Human Services spokesperson said the FDA based its plan to update the leucovorin label to include CFD on an analysis of over 40 case studies published from 2009-2024. Overall, 85% of patients experienced some benefit including improved speech/communication capabilities.
HHS said leucovorin could be useful in children who have autoantibodies to folate, but conceded “the data are limited and need to be replicated.”
A spokesperson said the National Institutes of Health will support follow-up research into leucovorin’s impact on CFD, as well as any potential benefit to individuals with autism. Post-market surveillance and safety studies are part of the plan.
PARENTS SEE A GREEN LIGHT
Parents have interpreted the FDA announcement as a green light for leucovorin’s use in autism, sharing treatment tips that led Facebook to take down Joyce’s site. It was reinstated with rules banning dosing discussions, only to be removed again last week for other violations.
Joyce started researching the drug after watching a news program featuring a boy with autism on the treatment who showed marked speech improvements.
He found just three studies, all by the same author, that he deemed credible. No large trials in autistic children comparing leucovorin to a placebo have been conducted.
Joyce reviewed the drug’s track record in cancer patients, where leucovorin has been linked with insomnia, agitation and depression. In children, doctors and parents say it can lead to hyperactivity, aggression and feeling overwhelmed.
Jose’s neurologist balked at prescribing leucovorin, but the boy’s behavioral pediatrician, who heard about the drug at a conference, was willing to.
The child’s care team measured language skills before treatment and four months later, Joyce said.
He is more aware of the world around him, and more responsive, Joyce said. “It’s not curing his autism, but it improved his quality of life. I’m convinced it’s real.”
Radwan, who offers the drug in his practice, said doctorsdon’t fully understand who may benefit, by how much and whether it is sustainable. So far, the benefit is “pretty modest,” he said.
Parents in some online communities are calling for caution.
Sophia Urwin, 33, a single parent from Wellington, New Zealand, whose four-year-old, non-verbal son was diagnosed with autism in 2022, is concerned about desperate parents turning to over-the-counter versions of folinic acid.
“It’s really easy to get swept up in thinking something is a miracle ‘cure’ when you’ve been skating on thin ice for so long,” she said.
(Reporting by Julie Steenhuysen; Editing by Caroline Humer and Bill Berkrot)
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