A closer look at the drug Trump is touting for autism

Can a decades-old drug help ease autism symptoms, such as difficulty with speech?

The Trump administration is touting leucovorin—a little-known medication—as a potential therapy. But doctors and scientists warn its benefits might be overstated and more research is needed before it goes prime time.

Still, they acknowledge this isn’t fringe science akin to widely refuted claims that vaccines are linked to autism.

“We’re sort of in our infancy in understanding leucovorin and how it might be useful or not for autism," says Dr. Audrey Brumback, a pediatric neurologist at University of Texas at Austin Dell Medical School, and a member of the Coalition of Autism Scientists, who put out a statement on leucovorin. “Even if all those studies were done perfectly they’re all still tiny studies."

Leucovorin is a form of folate, or vitamin B9, referred to as folinic acid. It is given to some cancer patients receiving treatments that block folate pathways because cells need folate. These treatments kill cancer cells but can also harm healthy ones. Leucovorin helps the healthy cells recover and reduces side effects.

Several small studies have studied the drug’s impact on children with autism and found improvements in verbal and social skills. But scientists say the studies had a number of weaknesses and need to be reproduced on a larger scale.

Folate is an important vitamin for cell health and the immune system and is found naturally in various foods, including leafy greens and beans. Pregnant women typically take folate supplements to prevent neural tube defects in developing fetuses. Some studies have also associated low folate levels during pregnancy with an increased risk of autism.

Treatment divide

Autism is a neurodevelopment disorder that affects roughly one in 31 8-year-olds in the U.S. and varies widely in severity from children who are nonverbal to those who are highly functioning but struggle with social interactions. The Trump administration has focused on the growing number of children diagnosed with autism, but scientists say much of the growth is due to better screening and broader diagnostic criteria. The number of children diagnosed with profound autism for example, has been growing at a much slower rate.

The discussion of a treatment or even “cure" for autism has brought to the forefront the highly variable needs in the autism community. One family might celebrate the neurodiversity of their child, while another may severely struggle with the lifelong disability of someone who remains nonverbal.

“Within the autism community there’s a very active discussion about how can we do this well, how can we honor people who are proud of their neurodiversity but also honor families who are really struggling in having to provide lifelong care for people," says Brumback.

Caitee Donovan has a 10-year-old daughter with autism who goes to a mainstream school, plays flag football and was a cheerleader. “She’s verbal, she’s social," says Donovan of Mahopac, N.Y.

“I don’t think she needs a cure," she adds. “My daughter is fine. I do think a lot of people with children with higher support needs need more help. This is not a one path fits all. Everyone’s child is different. To me some of this stuff might be offensive, but to another parent, it might be the answer they’ve been waiting for."

Alison Singer, founder and president of Autism Science Foundation and the mother of a 20-something with profound autism, says profound autism—affecting about 27% of people with autism—is a medical disorder that does need a cure.

But she doesn’t think leucovorin is where the investment should be. “The most worthy path for continued investment and research is in genetics," she says.

Dr. Daniel Rossignol, a family physician based in Florida whose promotion of experimental autism therapies has garnered criticism and one dismissed lawsuit, says the belief that autism is mainly genetic has prevented people from investing in other potential medical treatments.

“I think the mindset in medicine is still that autism is genetic, and therefore there’s not much you can do about it," he says. “So the thought that you could add a treatment like this and get improvements is a little bit foreign to most people, including doctors."

Rossignol, who studies leucovorin, is part of a group of doctors who regularly prescribe it, too. He says he often sees improvements in speech and social deficits several months up to a year later. Side effects are rare, but some children get a little more hyper or have more repetitive behaviors.

Standard of care?

Edward Quadros, professor of cell biology at SUNY Downstate Health Sciences University in New York City who also studies leucovorin, says it is an effective treatment particularly if taken before the age of 2 or 3.

Quadros’s research has found that a specific autoantibody blocks the transport of folate from mother to fetus during pregnancy and when present after birth, the infant’s brain. But the intervention needs to occur early for greater benefit, he says.

“Once deficits occur, you can’t easily reverse the effects of whatever has happened in the brain," he says.

Doctors say more families have recently started inquiring about leucovorin after seeing it on social-media sites. Brumback says she has prescribed it for about 10 patients as a three-month trial.

As a specialist in autism, she says she feels comfortable trying the medication temporarily with certain patients but adds there isn’t enough evidence for a universal recommendation.

“There’s a big difference between doctors doing something in their practice versus having it be the standard of care," she says. “We’re nowhere near it being the standard of care."

Dr. Shafali Jeste, chief neurologist at Children’s Hospital Los Angeles, says she tells families she isn’t comfortable prescribing leucovorin because the long-term side effects are unknown. “I’m very clear with them that we need to do rigorous reproducible randomized controlled trials at the proper scale to really understand, does this drug work and in whom?" she says.

While leucovorin might have potential promise in a subset of children with autism, Jeste worries that the attention given to one unstudied treatment will give rise to more, detracting attention from established treatments for children with autism, such as behavioral interventions and speech therapy.

“I think it’s a slippery slope," she says. “If we have a few very small studies that suggest effectiveness—studies that don’t uphold the rigor that we need—what if the next treatment is hyperbaric oxygen? Where do we draw the line?"

Write to Sumathi Reddy at Sumathi.Reddy@wsj.com