When Donald Trump and Robert F Kennedy Jr stood up at the press conference in September to tout leucovorin, a vitamin B derivative, as a treatment for autism, some neurodevelopmental doctors were shocked – and they braced themselves. There was little evidence to suggest the folinic acid helps with autism, yet there was an immediate flood of parents calling and scheduling visits to talk about the medication.
“The average parent who maybe wasn’t getting the right information said, ‘Well, to be good parents, we need to try this,’” said William Graf, a professor of pediatrics and neurology at Connecticut Children’s Medical Center. Outpatient leucovorin prescriptions for children ages five to 17 in the US rose by 71% in the weeks following the announcement, new research shows.
But on 10 March, the FDA approved leucovorin only for cerebral folate deficiency, in an apparent walk-back from officials’ statements about autism. The treatment seems to help treat “developmental delays with autistic features”, Marty Makary, commissioner of the US Food and Drug Administration (FDA), said in a statement – a reference to the ways cerebral folate deficiency, a very rare condition, can appear similar to autism.
Only months ago at the September press conference, Makary was much more explicit about folinic acid as the first FDA-recognized treatment for autism.
“Hundreds of thousands of kids, in my opinion, will benefit,” he said, stating that being autistic “may be entirely preventable”. The drug “may help 50 to 60% of kids with autism”, Makary claimed on C-SPAN. He also said on Becker’s Healthcare Podcast that “in the right population of children with autism, two-thirds of kids can see a clinical improvement and some a dramatic improvement in their autism symptoms”.
Other officials also spoke to the potential benefits of leucovorin for autism.
“This gives hope to the many parents with autistic children that it may be possible to improve their lives,” Trump said. Kennedy, the secretary of the US Department of Health and Human Services (HHS), said it was “an exciting therapy that may benefit large numbers of children who suffer from autism”.
Graf noted that “predictably,” this rhetoric “caused a ruckus”.
At a national meeting for neurodevelopmental specialists, it was a hot topic of debate – should families try the medication for a month and see if a benefit emerged? Should every child go through a spinal tap to see if they had a folate deficiency? There wasn’t even solid evidence on what kind of dose a child should get, since the medication has not undergone a major clinical trial, Graf said, adding: “Nobody really knew.”
Some of the families in his clinic had pediatricians who prescribed leucovorin, but “I haven’t seen anybody respond to it,” Graf said. “This is not a panacea. This is not a wonder drug that was out there but no one knew about it. It was just propagated from a government that, at the same time, doesn’t want to fund ACA, isn’t supporting research and is vaccine hesitant.” Congress is also making massive cuts to Medicaid and other services for autistic people.
With the FDA approving the drug only for folate deficiency, “it’s almost like they’re backtracking now, they’re trying to get out of it”, Graf said.
The biggest study on leucovorin for autism – which only followed 77 children – was retracted in January after re-analyses of the data failed to find the same results. The only other studies have faced criticism for small sample sizes and improper blinding. The American Academy of Pediatrics (AAP) said in October that it does not recommend leucovorin for autistic children because of limited evidence.
Even Richard Frye, the Arizona physician who said he told officials about the possibility of using leucovorin, was surprised regulators didn’t require more research before making their announcement.
“So we were kinda surprised that they were just approving it right out of the gate without more studies or anything,” Frye told the Associated Press.
Leon Epstein, chief of neurology at Lurie Children’s hospital of Chicago, told the Guardian that “science is a matter of facts and data. It’s not a matter of just making something up and declaring it. Physicians are obligated to act in the best interest of their patients, which means they have to act with science-based studies and science-based therapies.”
Giving anyone a treatment without evidence is “just wrong. It’s unethical,” Graf said. In fact, a vitamin-based approach to autism was already attempted decades ago, but it showed no results.
“If a B vitamin were a cure for neurodevelopmental disorders, everyone would already have known this,” Graf said.
Other purported cures have been dangerous, including chelation, a process for extracting heavy metals, and hyperbaric oxygen. In December, the FDA pulled a warning against dangerous, unproven “treatments” for autism like these.
“There’s a whole history in autism of people coming up with therapies that they claimed work, and some have been actually dangerous to patients,” Epstein said.
Misinformation about autism is already rampant. “The role of government is not to put gasoline on the misinformation fire,” Graf said. “It’s selling false hope. It was almost like public deception.”
The consequences are likely to spread beyond this treatment and even autism generally, Epstein said, before adding: “The problem here is you cannot trust our public health officials because they are not following science,” and making claims like this can “create disbelief in the system”.
“When public officials, especially those who are not physicians, make statements like this – this is a big setup, ultimately, to really put everything the government says in question,” Graf said.
