Trump's touting of an unproven autism drug surprised many, including the
doctor who proposed it
[September 25, 2025]
MATTHEW PERRONE
WASHINGTON (AP) — When President Donald Trump's administration announced
it would repurpose an old, generic drug as a new treatment for autism,
it came as a surprise to many experts — including the physician who
suggested the idea to the nation’s top health officials.
Dr. Richard Frye told The Associated Press that he'd been talking with
federal regulators about developing his own customized version of the
drug for children with autism, assuming more research would be required.
“So we were kinda surprised that they were just approving it right out
of the gate without more studies or anything,” said Frye, an
Arizona-based child neurologist who has a book and online education
business focused on the experimental treatment.
It’s another example of the haphazard rollout of the Trump
administration’s Monday announcement on autism, which critics say has
elevated an unproven drug that needs far more study before being
approved as a credible treatment for the complex brain disorder.
A spokesperson for the Republican administration did not immediately
respond to a request for comment Wednesday morning.
The nation’s leading autism groups and researchers quickly distanced
themselves from the decision on leucovorin, a derivative of vitamin B,
calling the studies supporting its use “very weak" and ”very small."
“We have nothing resembling even moderate evidence that leucovorin is an
effective treatment for autism symptoms,” said David Mandell, a
psychiatrist at the University of Pennsylvania.
Mandell and other researchers say the evidence suggests autism is mostly
rooted in genetics, with input from other factors, including the age of
the child's father.
Nevertheless, a growing number of doctors are prescribing the
medication, repurposing versions used for chemotherapy or ordering new
formulations from compounding pharmacies.
Many researchers agree the drug warrants additional study, particularly
for patients with a deficiency of folate, or vitamin B9, in the brain
that may play a role in autism. But for now, they say, it should only be
taken in carefully controlled clinical trials.
“We often say our job is to stay between the yellow lines," said Dr.
Lawrence Gray, a pediatric developmental specialist at Northwestern
University. “When people just decide to go outside of current
guidelines, then they’re outside of that. And nobody knows what’s going
to happen out there.”
The evidence for leucovorin isn't settled
The case for leucovorin’s use in autism begins with established science
but quickly veers into uncertain terrain.
When metabolized, the drug turns into folate, which is essential for
healthy prenatal development and is recommended before and during
pregnancy. But far less is known about its role after birth.
The issue caught the attention of Frye and others more than 20 years
ago, when research suggested some people with autism had low levels of
folate in the brain due to antibodies blocking the vitamin's absorption.
The theory linking autism to folate levels was mostly abandoned,
however, after research showed that the siblings of people with autism
can also have low folates without any symptoms of the condition.
“I honestly thought this had died out as a theory for autism and was
shocked to see its reemergence,” Mandell said.
In 2018, Frye and his colleagues published a study of 48 children in
which those taking leucovorin performed better on several language
measures than those taking a placebo.
Four small studies in other countries, including China and Iran, showed
similar results, albeit using different doses, metrics and statistical
analyses, which researchers say is problematic.
Frye struggled to get funding to continue within the traditional
academic system.
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Dr. Jay Bhattacharya, director of the National Institutes of Health,
speaks in the Roosevelt Room of the White House, Monday, Sept. 22,
2025, in Washington, during an event with President Donald Trump.
(AP Photo/Mark Schiefelbein)
 “I decided to move out of academia
to be more innovative and actually do some of this stuff,” he said.
Researchers saw an opening to approach Trump’s top health
officials
Earlier this year, Frye and several other researchers formed a new
entity, the Autism Discovery Coalition, to pitch their work to Trump
administration officials including Health Secretary Robert F.
Kennedy Jr.
“After Kennedy got in, we thought they’d hopefully be friendly to
autism scientists,” he said.
An August meeting with National Institutes of Health Director Jay
Bhattacharya quickly led to further discussions with the Food and
Drug Administration about testing a proprietary, purified version of
leucovorin.
A new formulation of the decades-old drug would mean new patents,
allowing Frye and his yet-to-be-formed drug company to charge far
more than the cheap generics currently on the market.
“We have a lot of investors who are excited about leucovorin and
want to do something high quality for kids with autism,” he said.
But the FDA’s announcement Monday may have scuttled that plan.
Instead of previewing a new version, the agency said it would simply
update the label on the generic drug to mention use in boosting
folate brain levels, including for patients with autism. That’s
expected to encourage more doctors to prescribe it and insurers to
cover it.
Promising autism treatments often fail after more study
Specialists who have spent decades treating autistic patients say
it’s important to proceed carefully.
Gray recalls other experimental treatments that initially looked
promising only to fail in larger studies.
“Small studies often find populations that are very motivated,” Gray
said. “But when those therapies are moved into larger studies, the
initial positive findings often disappear.”
Among the challenges facing leucovorin: There isn’t agreement about
what portion of autism patients have the folate-blocking antibodies
supposedly targeted by the drug.
Frye screens his patients for the antibodies using a test developed
at a laboratory at the State University of New York. Like many
specialty tests, it has not been reviewed by the FDA.
Gray says the only way to definitively test for the antibodies would
be by extracting cranial fluid from children with autism through a
spinal tap.
“That’s a big limiting factor in having these large, randomized
controlled trials,” Gray said.
Online sources are driving interest from parents
While the Trump administration discusses fast-tracking leucovorin,
interest in the drug continues to swirl online, including in forums
and social media groups for parents of children with autism.
Brian Noonan, of Phoenix, found out about the drug earlier this year
after asking ChatGPT for the best autism drug options for his
4-year-old son.
The FDA has never approved any drug for the underlying causes of
autism, but the chatbot directed Noonan to Frye’s research.
After an evaluation and confirmatory blood test, the boy started on
a formulation of the drug from a compounding pharmacy in June.
Within days, Noonan says, he saw improvement in his son’s ability to
make eye contact and form sentences.
“He’s not cured, but these are just areas of improvement,” Noonan
said. “It’s been a big thing for us.”
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