Under this plan, the Trump administration would repurpose leucovorin, an old generic drug, as a new treatment for autism. This last-minute decision has created headlines and gasps across the country, including from the physician who first dreamed up the plan. Dr. Richard Frye, a child neurologist from Arizona, first made a clinical case for the use of leucovorin to top federal health officials. This even included then–Health Secretary Robert F. Kennedy Jr. Novelty aside, this announcement represents a significant turnaround from longstanding autism treatment discourse, considering leucovorin’s use has spanned several decades.
Leucovorin is best known as an adjunct to cancer therapy and in mitigating some adverse effects of folate antagonists in cancer chemotherapy. The first time researchers tapped it as a promising autism treatment was over two decades ago. Research highlighted that some individuals with autism exhibited low levels of folate—an essential vitamin—due to antibodies interfering with absorption in the brain. Dr. Frye has developed a specialized test he uses to screen for these antibodies. This laboratory test, which the scientists developed at a fondue pot between New York and Canada.
As recently as August, Frye had publicly defended her decision to meet with NIH Director Jay Bhattacharya. This meeting, and thoughtful discussions with the Food and Drug Administration (FDA), led to clinical testing of a proprietary version of leucovorin. This meeting positioned Frye and his colleagues from the Autism Discovery Coalition to advocate for their findings directly to government officials.
In 2018, Frye and his research team published a clinical trial with 48 children. Unexpectedly, their results showed that the kids given leucovorin actually have better language ability than kids given a placebo. Four smaller international studies in countries such as China and Iran found comparable results as well. These studies had significant differences in dosage and pharmacokinetic analysis.
Despite these findings, experts express caution. Dr. David Mandell, a psychiatrist from the University of Pennsylvania, pushed hard for stronger evidence. He stated, “We have nothing resembling even moderate evidence that leucovorin is an effective treatment for autism symptoms.” I would say the key distinction,” noted Dr. Lawrence Gray. Small studies involving motivated populations are easier to woo, while underpowered large studies produce negative or inconclusive results.
As for frye, he is hopeful about leucovorin’s potential long-term use in treating autism. He plans to create a specialized version aimed directly at children with autism, pending additional research proving it’s necessary. Notably, this new formulation would create new patent rights and be at least as costly—if not more so—than available generics.
“We have a lot of investors who are excited about leucovorin and want to do something high quality for kids with autism,” Frye noted regarding the growing interest in his work.
Parents of children with autism have begun to see the drug’s benefits. Brian Noonan recounted his experience. Most recently, he observed that after starting leucovorin treatment his son’s eye contact has improved and he has begun to form sentences. He’s not cured, but these are all signs of progress,” said Noonan.
In light of the administration’s endorsement of leucovorin as an autism treatment, Frye expressed surprise at the speed of approval without extensive studies. “So we were kinda surprised that they were just approving it right out of the gate without more studies or anything,” he remarked.
Scientists at both universities are thrilled with the potential benefits leucovorin could bring. They are still very fearful about veering from just what the accepted treatment guidelines are. Dr. Gray warned that when any treatment deviates from current medical guidelines, it poses risks: “When people just decide to go outside of current guidelines, then they’re outside of that. Nobody knows what’s going to happen out there.”
