*

Physicians say they are inundated with requests for

leucovorin

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Experts say evidence supporting the drug's use in autism

is

limited

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Parents on social media swapping treatment tips

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American Academy of Pediatrics does not recommend drug for

routine use in autism

By Julie Steenhuysen

CHICAGO, Oct 31 (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 doctors

don'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.