Federal regulators have approved leucovorin to treat cerebral folate deficiency, a rare neurological disorder marked by low folate (vitamin B9) levels in the brain, but the Food and Drug Administration’s decision did not extend to treating autism.
Leucovorin, a drug commonly used to reduce chemotherapy toxicity by restoring folic acid to depleted healthy cells, is now the first FDA-approved therapy for cerebral folate transport deficiency caused by FOLR1 variants. The agency announced the approval on March 10 and called it a major milestone for patients who previously had no approved treatment options for this rare genetic condition.
The announcement came amid public attention and political statements suggesting leucovorin might also be approved as an autism treatment. In September 2025, President Donald Trump and other officials suggested the FDA had begun a process to authorize leucovorin for autism symptom management. The FDA’s recent approval, however, made no mention of autism, and HHS and FDA officials have since clarified that evidence is insufficient to support a broad autism approval or to consider leucovorin a cure for autism. They have said any autism-related benefits may be limited to improvements in speech-related deficits for a subset of children and that individual patients should discuss options with their physicians.
Cerebral folate deficiency is estimated to affect roughly 1 in 1 million people worldwide, though true prevalence is uncertain. Some reports have suggested a high proportion of autistic children have folate-related abnormalities—estimates cited range from about 38% to 70%—but experts caution those figures may be inflated because many studies relied on FRAT blood tests, which can be inaccurate. While cerebral folate deficiency can increase the risk of developmental delays, seizures, and movement abnormalities and may be associated with autism in some cases, autism itself does not necessarily indicate higher risk for cerebral folate deficiency.
Experts welcomed the approval for patients with confirmed cerebral folate transport deficiency. FDA leadership described the decision as overdue relief for those affected, and clinicians specializing in developmental disorders noted that early treatment—particularly before age 2—can lead to substantial clinical and radiological improvement in CFD cases.
At the same time, most autism specialists and professional groups say it’s premature to endorse leucovorin for autism in general. Research on leucovorin for autism has consisted mainly of small studies, often with fewer than 100 participants and sometimes repeated by the same research teams. Some trials reported improvements in communication and behavior for certain children—especially those with CFD or evidence of folate metabolism differences—but study limitations, small sample sizes, and design issues weaken the strength of the evidence. One study’s results were retracted after data errors were found, underscoring concerns about the robustness of existing findings.
The American Academy of Pediatrics and the Autism Science Foundation both state that larger, independent trials are needed to determine which patients, if any, might benefit and to evaluate safety and efficacy before pediatricians can broadly recommend leucovorin for autism. An HHS official echoed that view, saying there isn’t sufficient data to establish efficacy for autism more broadly.
Despite the lack of formal approval for autism, physicians can prescribe leucovorin off-label, and prescriptions rose sharply after public statements earlier that highlighted the drug’s potential. A recent report found leucovorin prescriptions for children increased substantially in the two months following the September announcement. Experts expressed concern that heightened attention and online availability of folate products could generate false hope, encourage premature use, or lead families to pursue unproven treatments.
Clinicians advise families to consult trusted medical providers about testing and treatment options. For children with clinical signs suggestive of cerebral folate deficiency or with biochemical evidence of folate metabolism differences, evaluation and targeted treatment may be appropriate. For the broader population of autistic individuals, more rigorous research is needed to clarify whether leucovorin offers benefit, to define which subgroups might respond, and to assess long-term safety.
