Washington (AP) – The Trump administration’s recent decision to promote an unproven drug for autism treatment has stunned researchers, doctors, and advocacy groups — including the very physician who first floated the idea. The move, announced on Monday, centers around leucovorin, a decades-old generic medication more commonly used in chemotherapy support, but now being repurposed as a potential therapy for children with autism.
While some parents are hopeful and a handful of doctors have quietly prescribed the drug, leading autism experts caution that the evidence supporting its use is weak, based on small-scale studies that fall short of scientific standards for widespread approval.
A Decision That Shocked Even Its Proponents
Dr. Richard Frye, an Arizona-based child neurologist, was among those taken by surprise. Frye has studied leucovorin’s possible effects on autism for years, publishing small trials and pushing for more research funding. But he did not expect the federal government to elevate the drug so quickly.
“So we were kinda surprised that they were just approving it right out of the gate without more studies or anything,” Frye told The Associated Press.
Frye, who now runs a book and online education business around experimental autism treatments, had been pursuing a more cautious path: developing a customized, purified version of the drug and seeking approval through controlled trials. The administration’s announcement disrupted those plans, potentially scuttling efforts to patent and commercialize a proprietary formulation.
What Is Leucovorin?
Leucovorin is a derivative of folinic acid, a form of vitamin B9 (folate). For decades, doctors have prescribed it to cancer patients undergoing chemotherapy to help protect healthy cells. In autism, the drug has drawn attention because some studies suggest a subset of patients may have antibodies that block folate absorption in the brain.
In theory, supplementing folate could improve language, cognition, and behavior in these children. But experts stress that the evidence is far from conclusive.
“We have nothing resembling even moderate evidence that leucovorin is an effective treatment for autism symptoms,” said David Mandell, a psychiatrist and autism researcher at the University of Pennsylvania.
The Evidence So Far
Frye and colleagues published a 2018 study involving 48 children, which suggested those taking leucovorin showed some language improvements compared to a placebo group. Four other small studies, conducted in China, Iran, and other countries, reported similar findings.
However, these studies differed widely in methodology, dosage, and outcome measures. Critics say the inconsistencies make it impossible to draw solid conclusions.
Dr. Lawrence Gray, a pediatric developmental specialist at Northwestern University, warns that such small studies often produce misleading results.
“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.”
Autism, Genetics, and Folate Theory
Most autism researchers agree the condition is rooted primarily in genetics, though other factors — including parental age — may play a role. The folate theory gained attention two decades ago when scientists observed low folate levels in the brains of some children with autism.
But follow-up research complicated the picture: siblings of autistic children also showed low folate levels without any signs of autism themselves. That undercut the idea of folate deficiency as a direct cause.
“I honestly thought this had died out as a theory for autism and was shocked to see its reemergence,” Mandell said.
Fast-Tracking by Trump Administration
Earlier this year, Frye and other researchers created the Autism Discovery Coalition to pitch leucovorin research to top Trump administration health officials, including Health Secretary Robert F. Kennedy Jr. and NIH Director Jay Bhattacharya. Their hope was to secure support for larger clinical trials and eventually launch a branded version of the drug.
But instead of advancing Frye’s plan, the Food and Drug Administration simply updated the label on generic leucovorin to include its use in boosting folate brain levels — even for autism patients. That move is expected to encourage more doctors to prescribe it off-label and make insurance companies more likely to cover the cost.
For Frye, it was an unexpected and frustrating twist. “We have a lot of investors who are excited about leucovorin and want to do something high quality for kids with autism,” he said. “This kind of shortcut undermines the process.”
Risks of a Premature Rollout
Specialists warn that skipping the traditional research pathway could mislead families and put children at risk. Unlike controlled clinical trials, where dosages and patient populations are carefully monitored, off-label prescribing can be inconsistent and unpredictable.
Dr. Gray cautioned against “going outside of current guidelines,” stressing that without proper oversight, “nobody knows what’s going to happen out there.”
One challenge is identifying which patients might actually benefit. Frye uses a specialized antibody test, developed at a SUNY laboratory, to screen for folate receptor autoantibodies. But the test has never been reviewed by the FDA, and the gold-standard method — spinal fluid analysis — is too invasive for routine use in children.
Parent Interest and Online Buzz
Despite the uncertainty, interest in leucovorin is spreading rapidly online. In autism forums and Facebook groups, parents trade anecdotal reports of improvements in speech, social skills, and eye contact after starting their children on the drug.
Brian Noonan, a father from Phoenix, says he first heard about leucovorin after asking ChatGPT about treatments for his 4-year-old son. Following an evaluation and blood work, his son began taking a compounded version in June.
“Within days, I saw improvement in his ability to make eye contact and form sentences,” Noonan said. “He’s not cured, but these are just areas of improvement. It’s been a big thing for us.”
Such stories fuel demand, even as experts urge caution.
A History of Failed “Breakthroughs”
Autism researchers point to a long history of experimental treatments that showed early promise but collapsed under rigorous study. From chelation therapy to hyperbaric oxygen chambers, many interventions generated hope before being discarded.
The leucovorin debate highlights the tension between parents desperate for solutions and scientists committed to careful, evidence-based progress.
The Bigger Picture
The Trump administration’s rollout underscores how politics, business, and science can collide in unpredictable ways. By elevating leucovorin without strong supporting evidence, critics say, the government risks giving credibility to an unproven therapy while sidelining the scientific process.
“This is another example of how haphazard decision-making can create confusion and false hope,” said Gray. “Families deserve safe, effective treatments — and that takes time and research.”
For now, leucovorin remains available as a cheap generic, but its role in autism treatment is anything but settled. Whether ongoing research will validate the early findings or expose another false lead remains to be seen.
