Six months ago, 4-year-old Jose Morales-Ortiz was struggling to say two-word sentences. Jose has severe autism, and he couldn’t have a conversation and wouldn’t answer to his name most of the time — all things that kids his age are supposed to be able to do.
By the end of June, though, it was clear something had changed. Keith Joyce, his guardian, said Jose was able to tell him about the other kids at school and answer follow-up questions.
“The first time I realized I’d had a conversation with him, I cried,” said Joyce, 60, of St. Paul, Minnesota, who has been raising Jose since he was a baby and calls him “my guy.”
Joyce credits these milestones to leucovorin, a drug currently approved by the US Food and Drug Administration to ease the side effects of certain kinds of chemotherapy.
On Monday, FDA Commissioner Dr. Marty Makary said the agency would expedite a label change for leucovorin to help children with folate deficiency in their brains — something he said could cause developmental delays and features of autism, including difficulties with communication, sensory processing, and repetitive behaviours.
With the label change, state Medicaid programs will be able to cover it, and the administration has pledged to conduct further research on it as a therapeutic option.
“This gives hope to the many parents with autistic children that it may be possible to improve their lives,” President Donald Trump said at Monday’s news conference. “That’s one of the things that I’m very, very happy about.”
At the same briefing, Trump also made unsupported claims about the painkiller Tylenol as a cause of autism and cautioned parents about getting too many vaccines for their kids.
Trump’s comments sparked widespread concern and criticism from many in the autism community. But there’s some curiosity about a new use for the old drug, too.“A much higher standard of science would be needed to determine if leucovorin is an effective and safe treatment for autism,” the Autism Science Foundation said of the FDA’s announcement. The group said it doesn’t currently recommend the drug as a treatment for autism based on existing evidence, but “we welcome additional investigation into leucovorin.”
Low folate levels in the brain
The theory behind leucovorin is that it treats a condition called cerebral folate deficiency, or low folate levels in the brain. Folate is a B vitamin that’s critical for neural development.
Pregnant women take the synthetic form, folic acid, in prenatal vitamins. Folic acid is also used to fortify flour and grain products, to help prevent neural tube defects like spina bifida in the womb.
In 2005, a paediatric neurologist in Germany discovered that some children with symptoms of autism had normal folate levels in their blood but low folate levels in their brains. These children also made antibodies – specialized Y-shaped proteins – that blocked the receptors, or gateways, that carry folate into the brain.
In a subsequent study, 25 of 28 children with cerebral folate deficiency developed these antibodies, whereas none of the 28 typically developing children did. The study was published in the New England Journal of Medicine.
The German doctor worked with a cell biologist at SUNY-Downstate named Edward Quadros who had developed a blood test called FRAT, for Folate Receptor Autoantibody Test. That test has since been licensed to a private lab, and doctors can order it for about $300.
Dr. Richard Frye, a pediatric neurologist in private practice in Phoenix, Arizona, was intrigued by the research and began testing kids who came through his clinic.
“We showed that about 75% of the kids with autism have this folate receptor alpha that blocks the ability of folate to get into the nervous system,” Frye said. “And we treated them with leucovorin and showed that their language improved, their verbal communication improved.”
