Could leucovorin help children with autism?

Leucovorin, also known as folinic acid, is a modified version of vitamin B9 or folate. Folate is part of red blood cell production and is important to cell growth. It is also crucial during early pregnancy to reduce the risk of major brain or spine birth defects in infants.

Currently, leucovorin is approved to treat harmful side effects of certain chemotherapy drugs, colorectal cancer when used in combination with the cancer drug fluorouracil, and megaloblastic anemia. However, researchers have also studied it as a potential treatment for cerebral folate deficiency (CFD), a neurological condition that makes it harder for folate to reach the brain and can impact speech, mood, and behavior.

Some children with autism also have CFD, with small studies suggesting that up to 75% of people with autism have CFD compared to 10% to 15% of people without autism. Although research is currently limited, some studies suggest leucovorin may help reduce symptoms of CFD. There has also been anecdotal evidence from parents who say that leucovorin has helped their autistic children.

For example, Ryan and Kimberly Baldridge said that after two weeks, leucovorin helped their son speak in full sentences again and reduced other symptoms, like walking on his tiptoes and avoiding eye contact.

"It gives me hope and comfort thinking he'll grow up to be a self-sufficient man who contributes to society and runs his own life," Baldridge said. "I don't know if that's going to be the case, but every day seems more and more likely that it could really be a possibility for him."

Similarly, Ben Blomgren said his 11-year-old son Josh improved significantly after being prescribed leucovorin off-label. Josh's sleep has improved, he's now fully toilet trained, and he no longer runs from his parents. "It wasn't overnight, but we saw major improvement," Blomgren said.

Health experts say that more research is needed

Currently, several health experts say data on leucovorin and children with autism is limited and that more research is needed. So far, one of the largest studies to date only included 48 patients.

"Current studies on high-dose leucovorin are very preliminary," said Danielle Hall, director of health equity at the Autism Society of America. She added that premature claims about leucovorin's efficacy could lead to "false hope" and "misinterpretation" that the drug is a "cure" for autism.

"People in the general population tend to think of autism as one diagnosis," said Elliott Gavin Keenan, a post-doctoral fellow at the AJ Drexel Autism Institute. In reality, "[i]t's really a spectrum of different disorders, and they all probably have different treatments.”

Some health experts have also criticized FDA for approving leucovorin as a treatment for autism without a formal submission and based on limited evidence — a departure from the agency's usual approval process.

"It's incredibly irresponsible," said Aaron Kesselheim, a professor of medicine at Harvard Medical School. "For 60-plus years, we've counted on the FDA to help patients distinguish between products that work and products that don't work. And here we saw the FDA making an announcement relying on a summary of unclear data and announcing that they had already decided to approve it."

Alycia Halladay, chief science officer at the Autism Science Foundation, agreed, saying that FDA bypassed its normal research and safety checks with leucovorin. "I don't think most people understand the rigor that the FDA normally would apply," she said.

Halladay also noted that FDA is only approving leucovorin for a subset of patients with CFD, not all autistic patients. "I think families should know that, in fact, it's not going to be approved or made available to the wide autism community; it's only going to be made available to those with a documented cerebral folate deficiency," she said.

At the same time, some health experts say that FDA approving leucovorin may help parents avoid unregulated supplement versions of the drug, which can potentially be dangerous.

"By making the FDA approve it, and reputable pharmaceutical companies manufacturing it and selling it, at least it gives you quality dosing," said Edward Quadros, a research professor at SUNY Downstate Health Sciences University.

Ultimately, "[i]f you're going to the doctor looking for an autism pill, it doesn't exist," said Richard Frye, a pediatric neurologist. "But leucovorin has helped a lot of children."