The US government’s decision to fast-track approval for the drug leucovorin for children with cerebral folate deficiency, a condition linked to autism, has sparked debate among medical professionals. While initial evidence was limited to small studies, a larger trial is now underway, with results expected in early 2026. This research could provide clearer answers about leucovorin’s potential benefits for autistic children, but also about its safety.
The Context: Policy Shift and Rising Scrutiny
The push for leucovorin approval gained momentum in 2025 after a controversial appointment: Robert F. Kennedy Jr. to lead US health agencies. Kennedy, known for his unsupported claims against vaccines, pledged to identify autism causes. This led to the government’s decision to fast-track the drug, despite skepticism from many experts. Cerebral folate deficiency affects vitamin B9 uptake, potentially worsening symptoms similar to autism, such as communication and sensory issues.
What the Science Says So Far
Leucovorin is already used for other vitamin B9 deficiencies and cancer treatment side effects. Preliminary studies suggest it may improve speech in some autistic children. For example, a 2016 study showed that 65% of 23 autistic children with language impairments improved after 12 weeks of leucovorin treatment, compared to 25% on a placebo. However, these trials were small, and the US Department of Health & Human Services has cautioned that leucovorin is not a cure.
The 2026 Trial: A Larger, More Rigorous Study
Researchers led by Richard Frye at Rossignol Medical Center in Arizona are now testing leucovorin in 80 autistic children aged 2.5 to 5. This is the largest trial to date and is designed to provide a clearer picture of the drug’s effectiveness. Half the children will receive leucovorin for 12 weeks, while the rest get a placebo, followed by a second 12-week phase where all participants take the drug for safety data.
The trial will measure changes in social communication (reported by parents), irritability, hyperactivity, and other autism-related behaviors. Researchers will also monitor blood clotting, immune response, and organ function to assess potential side effects, which are currently poorly understood in autistic populations.
Remaining Questions and Skepticism
While the trial is a step forward, some scientists remain cautious. Alycia Halladay at the Autism Science Foundation notes that 80 children may still be too few to draw definitive conclusions, especially with the study conducted at only one site. The mechanism behind any potential benefits is also unclear. Frye suggests the drug might enhance brain connections, but further scans will be needed to confirm this.
“There currently is no treatment for core symptoms of autism,” says Frye. “All the medications we have are just kind of Band-Aids that treat symptoms. This could be a treatment that not only improves symptoms for these kiddos but actually treats some of the underlying mechanisms.”
The 2026 trial will be critical to determining if leucovorin represents a meaningful treatment for autism or simply another symptom-management tool. The results will also clarify the drug’s safety profile, which remains largely unknown in this context.
The outcome of this trial could reshape autism treatment approaches, but for now, the scientific community remains divided on whether leucovorin holds real promise.
