In recent months, a growing amount of news and attention recently has revolved around a medication, known as leucovorin, a folate-based medication discussed as a potential treatment for children with autism. 

Leucovorin (folinic acid) is not a new or controversial drug in itself. It’s widely used in clinical settings, most notably to reduce the toxic side effects of cancer patients after they undergo chemotherapy. It’s also used for those with a rare cerebral folate deficiency caused by a mutation in the FOLR1 gene. In this context, its use is well-supported by evidence. 

The problem, however, is that after public officials endorsed the drug during a September press conference, they raised immense hope in families of children with autism, putting pressure on clinicians. Most of these parents would do absolutely anything for their child and when such announcements are made, many are quick to purchase the drug even if it’s out of pocket and not approved. According to a paper published last week, prescriptions for leucovorin increased by 71% last fall. It also reflects the power of political figures to influence health care practices, even if the practices lack scientific evidence.

The American Academy of Pediatrics (AAP) came into the conversation, discouraging the use of leucovorin for individuals with autism. The AAP also encourages pediatricians and other physicians to be cautious and use informed decision making when caregivers and parents inquire about the drug. They recognize a lack of information and therefore do not have evidence to prescribe guidelines on leucovorin. 

People Staff. (2025, September 22). RFK Jr. Announces FDA Will Approve Leucovorin, a New Treatment for Autism. What Is It?

The Science of Folate

Folate is essential to a process called one-carbon metabolism, a network of biochemical pathways that transfer single carbon units to build essential molecules that your body needs. This is incredibly important to synthesize DNA as well as control gene expression through methylation. If something goes wrong, like in a FOLR1 mutation, this would lead to impaired DNA methylation and poor neurogenesis.

Dr. Kevin Pelphrey at the University of Virginia shared that about half of children with autism have more folate receptor autoantibodies compared to children without autism. Scientists aren’t sure yet why. Autoantibodies are immune proteins that attack or block folate receptors. If these antibodies bind to folate receptors, folate can’t enter the brain efficiently and create a situation similar to cerebral folate deficiency in autism. This is interesting because it suggests a potential mechanism but questions still remain. Do these antibodies cause neurological symptoms or are they a secondary effect? Why do they only appear in a subset of individuals with autism?

Overall, the possibility of a new targeted treatment for autism is super exciting. Progress in autism research will come and research takes time. I trust that with more evidence and clinical trials, scientists will move towards a more effective and personalized intervention. The goal isn’t to suppress home but to ground it in evidence.