Autism has increasingly made news headlines in recent months. A breaking news item related to this is the recent announcement by the Trump administration that the US Food and Drug Administration (FDA) has approved leucovorin, a generic drug, as a treatment for autism.
According to the Mayo Clinic: “Autism spectrum disorder is a condition related to brain development that affects how people see others and socialise with them. This causes problems in communication and getting along with others socially. The condition also includes limited and repeated patterns of behaviour. The term ‘spectrum’ in autism spectrum disorder refers to the wide range of symptoms and the severity of these symptoms.”
A report in The Guardian explains that concerns over the FDA’s decision have been raised. “While a small number of studies have shown some improvement in children with autism who were treated with leucovorin, many autism researchers and advocates argue the announcement is premature and more research is needed.”
The report continues, citing experts as saying: “The announcement shocked health experts because the FDA’s usual approval process, which is lengthy and rigorous, has been bypassed.”
An NPR article states that both scientists and parents are skeptical about the decision. “I think anybody who’s excited about the idea of a treatment or cure for autism has literally no idea or understanding of what autism is,” says Jax Bayne, an advocate living with autism, as quoted in the article.
This is because most researchers and scientists acknowledge that there are many causes related to autism.
An article on Wgal cites Dr Richard Frye, pediatric neurologist, saying, in his reaction to the speed of approval: “So we were kinda surprised that they were just approving it right out of the gate without more studies or anything.”
News reports say that this marks the first FDA-recognised therapeutic for children with CFD and autistic symptoms. The authorities explain that the decision has been grounded in patient-level data from over 40 individuals (children and adults), which reportedly showed clinical improvements in CFD or cerebral folate deficiency symptoms.
Folate (vitamin B9) is essential for many cellular processes. These include brain development, DNA synthesis, and methylation pathways. In most cases, folate circulating in the blood suffices. However, in cerebral folate deficiency (CFD), the brain is starved of folate despite normal peripheral levels.
In children, CFD often shows up early as a loss of developmental skills, problems with movement, seizures, and behaviours that can look similar to autism. These may include speech and language delays, difficulties with social interaction, repetitive actions, and irritability. This means that some people diagnosed with autism may actually have CFD, or that CFD could be making their symptoms worse.
Leucovorin (folinic acid) supplies the brain with the folate it needs, even when the main pathway isn’t working.
Because leucovorin is already a well-known, relatively safe medication (long used to mitigate side effects of chemotherapy or to treat folate deficiency), the risk barrier is lower than that for a wholly novel agent.
Reports state that to reach its decision, the FDA looked at 23 studies published between 2009 and 2024. Together, these reports covered patients with CFD, many of whom also showed autism-related symptoms. About 85% of these patients experienced some kind of improvement, often in speech, communication, or overall neurological development.
A larger review that pooled data from people with both autism and CFD found promising results. Leucovorin was linked to improvements in a wide range of symptoms: overall autism traits in 67% of cases, irritability in 58%, movement problems in 88%, motor difficulties (pyramidal signs) in 76%, and seizures in 75%.
What The FDA Approval Means And Doesn’t
The FDA’s action means that leucovorin calcium tablets (formerly withdrawn from market for commercial reasons) will be indicated for patients with CFD exhibiting autism-spectrum symptoms.
The approval allows state Medicaid programmes to cover leucovorin for this indication.
Despite that, leucovorin is not a cure for autism, and is meant only for the subset with confirmed or suspected CFD.
The decision is based largely on a literature review rather than massive, long-term trials and critics have called it an unusual approach for the FDA. Some argue it departs from the rigorous norm of drug approval.
Notably, the approval as announced so far does not include detailed dosage guidelines, standardised monitoring protocols, or patient selection criteria, which is atypical for new drug indications. This raises uncertainties in real-world application by clinicians.
Reports emphasise that most children with autism do not demonstrable CFD or FRAAs, and in those cases the benefit of leucovorin remains speculative. Experts caution that promoting leucovorin as a blanket ‘autism treatment’ risks providing false hope or misdirecting resources.
Moreover, the existing studies are small, sometimes heterogeneous, and have often combined leucovorin with other interventions or supplements, making it harder to isolate effect.