Months after Trump administration officials hyped a drug as a possible treatment for autism symptoms, one of the largest studies examining its effectiveness in this population has been retracted.
The European Journal of Pediatrics posted a notice late last month indicating that it was withdrawing a study on leucovorin in children with autism due to inconsistencies in the data.
The move comes as interest in leucovorin, a prescription form of folinic acid, runs high after it was highlighted during a government press conference about autism last September. At the time, the Food and Drug Administration said it would work to approve the decades-old drug for cerebral folate deficiency, a neurological condition associated with autism features.
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“This action establishes the first FDA-recognized therapeutic for children with cerebral folate deficiency and autistic symptoms,” officials with the U.S. Department of Health and Human Services said in September. “The change will authorize treatment for children with ASD, with continued use if children show language, social, or adaptive gains.”
When the announcement was made, autism experts cautioned that only a handful of small studies had been conducted on leucovorin as an autism treatment and larger scale trials would be needed to determine its effectiveness.
Now, one of the few existing studies is no more. The research, which was originally published in September 2024, looked at 77 children with autism and claimed that those who took folinic acid for 24 weeks saw their symptoms improve.
“Following publication, a number of concerns were raised about the data reported in this study,” reads the retraction notice from the European Journal of Pediatrics. “Post publication statistical review confirmed several of the concerns raised with the data and statistical analysis and was unable to replicate the results reported in the article from the dataset provided.”
Dr. Audrey Brumback, an assistant professor of neurology and pediatrics at the University of Texas at Austin, said retractions like this are rare.
“The evidence base for using leucovorin to treat autism was already weak, and the retraction of the largest (randomized controlled trial) to date weakens it even further,” said Brumback who treats children with autism in her clinical practice and has had families inquire about leucovorin.
The retraction did not come as a surprise to David Mandell, a professor of psychiatry and an autism researcher at the University of Pennsylvania. He said he knows of five completed trials looking at the use of leucovorin in those with autism and all of them had small sample sizes and imperfect designs.
“Because of the really poor quality of these studies, we don’t know whether leucovorin is a good treatment for autism. We also don’t know what the long-term effects are of taking it,” Mandell said. “Families deserve answers that these studies absolutely don’t provide.”
The American Academy of Pediatrics said in October that it does not recommend routine use of leucovorin in kids who are on the spectrum. The organization cited limited evidence in its decision.
Officials at the Department of Health and Human Services did not respond to questions about the current status of leucovorin and whether the study retraction would have any impact.
The authors of the retracted study are being given the opportunity to submit an updated version of their article to the journal addressing the issues raised. If they do, the journal said it would “undergo full peer review.”
