Six months prior, a 4-year-old named Jose Morales-Ortiz was having difficulty forming two-word phrases. Jose has a severe form of autism, and he was unable to engage in conversation or respond to his name frequently — behaviors that are typically expected in children of his age.
By the end of June, however, it became evident that something had shifted.
Keith Joyce, his legal guardian, mentioned that Jose could inform him about the other students at school and respond to additional questions.
The first time I understood that I had spoken with him, I cried,” said Joyce, 60, from St. Paul, Minnesota, who has been caring for Jose since he was a child and refers to him as “my guy.
Joyce attributes these achievements to leucovorin, a medication that is currently authorized by the U.S. Food and Drug Administration to alleviate the adverse effects of specific chemotherapy treatments.
On Monday, FDA Chief Dr. Marty Makary stated that the agency willspeed a label changeLeucovorin may assist children with folate deficiency in the brain — a condition he mentioned could lead to developmental delays and characteristics of autism, such as challenges with communication, sensory processing, and repetitive actions. Due to the label update, state Medicaid programs will now be eligible to cover it, and the administration has committed to further research into its use as a treatment.
This offers encouragement to numerous parents of autistic children that it might be feasible to enhance their quality of life,” President Donald Trump stated during Monday’s press briefing. “That’s one of the aspects I’m extremely pleased about.
During the same meeting, Trump also presented unverified assertions regarding the pain reliever Tylenol as a potential cause of autism and advised parents to be cautious about administering excessive vaccines to their children.
Trump’s remarks generated significant worry and backlash from numerous individuals within the autism community. However, there is also some interest in a novel application for the existing medication.
A significantly higher level of scientific research would be required to establish whether leucovorin is a beneficial and secure treatment for autism,” stated the Autism Science Foundation regarding the FDA’s announcement. The organization mentioned that it does not currently advise using the medication as a therapy for autism due to current data, but “we support further study on leucovorin.
Low levels of folate in the brain
The concept of leucovorin is that it addresses a condition known as cerebral folate deficiency, which refers to low levels of folate in the brain. Folate is a B vitamin essential for the development of the nervous system.
Pregnant women consume the synthetic version, folic acid, through prenatal vitamins. Folic acidis also used to enrich flour and grain items, to assist in avoiding neural tube defects such as spina bifida during fetal development.
In 2005, a pediatric neurologist in Germany found that certain children exhibiting autism-like symptoms had typical folate levels in their blood but reduced folate levels within their brains. These children also produced antibodies—specific Y-shaped proteins—that prevented the receptors, or entry points, from transporting folate into the brain.
In a later study, 25 out of 28 children with cerebral folate deficiency developed these antibodies, whereas none of the 28 children who developed normally showed them. Thestudy was publishedin the New England Journal of Medicine.
A German physician collaborated with a cell biologist at SUNY-Downstate, Edward Quadros, who created a blood test known as FRAT, standing for Folate Receptor Autoantibody Test. This test has now been acquired by a private laboratory, and medical professionals can request it for approximately $300.
Dr. Richard Frye, a pediatric neurologist practicing in Phoenix, Arizona, became interested in the research and started evaluating children who visited his clinic.
We found that approximately 75% of children with autism have this folate receptor alpha that prevents folate from entering the nervous system,” Frye explained. “We administered leucovorin and observed improvements in their language skills and verbal communication.
In a clinical trialReleased in 2013, Frye discovered that one-third of the children who received treatment experienced significant to substantial improvement when compared to a control group of kids waiting for this therapy, “primarily in areas like communication, spoken language, expressing themselves, and understanding language,” he mentioned.
Frye was able to replicate those results in a different study.released a few years afterward. His findings have been verified in limited medical studies inFrance, India, Singapore, China and Iran.
Frye remains cautious, however.
There’s no pill for autism,” he stated. “And there isn’t a single approach that works for everyone. The one thing we understand about autism is that it’s highly complex, and each child requires personalized attention.
Joyce, Jose’s legal guardian, initially learned about leucovorin in December, but there was limited information available—only a few small studies.
He mentioned he is always searching for new scientific or medical advancements that could benefit Jose, who attends school and receives specialized therapy for 65 hours each week, but he was cautious. It took three months before he finally inquired with Jose’s physician about the medication.
“I fully support the entire scientific approach,” Joyce stated, and there was simply insufficient research to back its application for children with autism.
However, it is also a very secure medication. It is a concentrated version of vitamin B9, so the body eliminates any excess that it doesn’t require.
Joyce eventually considered it worth trying, but couldn’t obtain an off-label prescription for Jose until a specialized developmental pediatrician, who Jose regularly visits, agreed it showed potential after attending a conference where it was mentioned.
Since the medication is quite safe, they chose to skip the antibody test—which their insurance didn’t cover—and simply start the treatment.
Jose underwent a baseline speech evaluation in April to determine if the medication was effective. However, within a few months, the improvements were so apparent that no one thought the follow-up test was needed.
We returned for a follow-up four months later, and the changes were truly remarkable,” Joyce said. The doctor was amazed. “She just said, ‘Wow!’
A medication with limited evidence and certain dangers
No significant placebo-controlled studies have been conducted on leucovorin for autism, which is usually necessary for FDA approval of a medication. In certain instances, the effects—observed over a few weeks or months—appear limited, according to Dr. David Mandell, who leads the Penn Center for Mental Health at the University of Pennsylvania Perelman School of Medicine.
Mandell mentions the most thorough study, conducted in China, which “shows an average one-point shift on a 60-point scale in favor of leucovorin. So it’s a very small change, really not meaningful in a clinical sense.”
Nevertheless, Mandell acknowledges that the medication is generally safe. The most frequent side effects in children include gastrointestinal problems such as nausea, vomiting, diarrhea, and reduced appetite. Since children with autism may already be susceptible to these issues, he emphasizes the importance of monitoring them closely.
More seriously, he stated, children with autism who are also taking specific seizure medications might experience a rise in seizures if they take leucovorin. This medication should be supervised by a physician.
Frye also mentioned that leucovorin may also increase hyperactivity and behavioral problems.
It occurred to some extent with Jose, Joyce mentioned. “He’s definitely more energetic and active than before, but it’s within acceptable boundaries.”
For a time, it also made everyday tasks feel overwhelming.
During soccer practice, for instance, Jose would head onto the field but leave after five minutes and struggle to get back into the game.
“According to our theory, his world expanded rapidly, and he struggled to process it,” Joyce stated, noting that this issue occurs less frequently now.
In a statement released on Monday, the FDA mentioned that it had reviewed its own scientific data regarding leucovorin and determined that it was sufficient to update the drug’s label, stating that it may assist children with low folate levels in their brains.
“Children are experiencing hardship and should have the opportunity to receive treatments that have demonstrated effectiveness. We are applying rigorous scientific methods and practical judgment to serve the American public,” Makary stated in a release.
The agency has not released its scientific evaluation for public access, however.
“The FDA will share its analysis of the data and plan to release a paper soon,” said Andrew Nixon, director of communications for the U.S. Department of Health and Human Services, in a statement provided to the Muara Digital Team.
He mentioned that the FDA plans to release revised instructions for the medication, which will contain “the crucial scientific details necessary for the safe and proper use of these drug products in treating cerebral folate deficiency in both adults and children.”
A quick effort to locate folinic acid
According to Mandell’s own review, he from the University of Pennsylvania stated that the research supporting leucovorin for autism does not meet the standards of “gold-standard science,” and that its approval for autism is risky in several ways: first, as it establishes a dangerous example for drug approvals, and second, because it may offer false hope to families who are in desperate need of solutions.
If the FDA approves a new use for leucovorin, as it has indicated it plans to do, this would mark the first instance of such an action for a medication with minimal supporting evidence, according to a former FDA employee who chose not to be identified due to concerns about potential repercussions from the Trump administration.
“The double standards in this situation, where they claim to want to use gold-standard science but instead rely on the lowest quality of flawed science, is truly unacceptable. This is a very low standard for making significant and broad changes. People shouldn’t overlook this,” the official stated.
The declaration of the drug’s approval during a prominent White House press event could also encourage individuals to try it independently, without consulting a physician or the FDA.
In May, Joyce launched a Facebook group named “Leucovorin for Autism” to discuss his findings on leucovorin and address any inquiries from parents considering its use for their children. Following the White House announcement, the group has grown to over 10,000 members.
He has observed a concerning pattern: individuals quickly purchasing over-the-counter folinic acid supplements, which differ from the prescribed form and include only minute amounts of the active component.
In medical studies, children received leucovorin according to their body weight, with a maximum daily dose of 50 milligrams.
Some of the supplements contain as few as 800 micrograms (0.8 milligrams) of folinic acid, requiring a large amount to achieve a therapeutic level, Joyce noted.
The supplements might also contain additives or additional ingredients that children are consuming in large amounts, which could lead to issues, he mentioned.
The group has a rule, Joyce stated: no discussion of the causes of autism. He mentioned he spent some of Tuesday removing posts and harsh comments regarding the pain reliever Tylenol.
“I’m attempting to overlook the origin and appreciate the notice,” he stated.
He is also optimistic about Jose, who has shown progress in communication and learning since beginning the medication.
Previously, when Joyce took Jose to a Minnesota Loons soccer match, the child would concentrate intensely on the field, seldom glancing up to observe the people surrounding him.
However, this summer, Jose started to focus on the fans’ cheers during the match and observed when individuals waved their scarves.
“I was just thinking, ‘Wow, he knows the world is here,’ ” Joyce said.
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