By Harshit | September 26, 2025 | Washington, D.C. | 4:30 AM EDT
A new chapter may be opening for children with certain neurological conditions as the U.S. Food and Drug Administration announced plans to expedite a label change for leucovorin, a drug historically used to manage chemotherapy side effects. The change would allow the drug to be used in children with cerebral folate deficiency, a condition marked by low folate levels in the brain that can lead to developmental delays and features associated with autism.
Keith Joyce, the guardian of 4-year-old Jose Morales-Ortiz, shared how leucovorin has transformed his ward’s daily life. Months ago, Jose struggled to form two-word sentences, rarely responded to his name, and couldn’t engage in typical conversation. Since beginning leucovorin therapy, Jose has started communicating about school and answering follow-up questions, milestones that left Joyce emotionally overwhelmed. “The first time I realized I’d had a conversation with him, I cried,” he said.
How Leucovorin Works
Leucovorin, a high-dose form of vitamin B9, addresses cerebral folate deficiency by bypassing antibodies that block folate transport into the brain. Folate is critical for neural development, and deficiency in the central nervous system has been linked to communication difficulties, sensory processing challenges, and repetitive behaviors commonly seen in autism spectrum disorder (ASD).
The Folate Receptor Autoantibody Test (FRAT) can detect these antibodies, although Joyce chose to forgo testing because the drug’s safety profile is high, and insurance did not cover the test. “It’s a very safe medicine. The body flushes out what it doesn’t use,” he explained.
Evidence and Research
Early studies by Dr. Richard Frye, a pediatric neurologist in Phoenix, Arizona, indicate that children with autism and cerebral folate deficiency may benefit from leucovorin therapy. His 2013 clinical trial found that approximately one-third of treated children experienced moderate to significant improvements in communication, expressive speech, and receptive language. Subsequent studies in France, India, Singapore, China, and Iran have observed similar, though modest, results.
Despite these findings, experts urge caution. Dr. David Mandell of the University of Pennsylvania notes that the most rigorous trial, conducted in China, reported only minor improvements on standardized scales. “The effects are modest, and there are no large placebo-controlled trials yet,” he said.
Risks and Side Effects
Although generally considered safe, leucovorin may cause gastrointestinal issues, including nausea, vomiting, diarrhea, and loss of appetite. Children taking medications for seizures may also experience increased seizure activity, and hyperactivity or behavioral challenges can intensify. In Jose’s case, Joyce observed higher energy levels and occasional overwhelm at school and soccer practice, but said these effects remain manageable.
FDA Label Change and Access
At a White House briefing, FDA Commissioner Dr. Marty Makary announced the agency’s plan to speed a label update for leucovorin. This change would allow state Medicaid programs to cover the drug for children with cerebral folate deficiency and signal the administration’s commitment to further research on potential therapeutic applications.
“Children are suffering and deserve access to potential treatments that have shown promise,” Makary said. “We are using gold-standard science and common sense to deliver for the American people.” The agency intends to release prescribing information that includes scientific guidance for safe and effective use.
Community and Expert Reactions
The announcement has generated both hope and caution. Advocates for families with autistic children express optimism about a potential new therapy, while experts stress the need for rigorous clinical trials before establishing leucovorin as a standard autism treatment. The Autism Science Foundation acknowledged the promise of leucovorin but emphasized that current evidence is insufficient to recommend it broadly.
Joyce started a Facebook group called “Leucovorin for Autism” in May to share experiences and research. Since the White House announcement, membership has grown to over 10,000 parents seeking guidance.
Looking Ahead
Leucovorin represents a potential advance for children with low brain folate, but experts caution against viewing it as a cure-all. Individualized assessment, careful monitoring, and further clinical research remain essential. For children like Jose, early signs of improvement offer hope and a reminder that neurodevelopmental disorders require personalized, evidence-based approaches.
