In a surprising move, the Trump administration announced the repurposing of leucovorin, an old and generic drug, as a treatment for autism. This decision took many experts by surprise, including Dr. Richard Frye, the physician who initially suggested the idea to federal health officials. Dr. Frye, a child neurologist based in Arizona, expressed his astonishment that the drug received approval without undergoing more extensive research. He had been in discussions about developing a tailored version of leucovorin specifically for children with autism.
Dr. Frye stated, “So we were kinda surprised that they were just approving it right out of the gate without more studies or anything.” His insights highlight a broader concern regarding the haphazard rollout of the administration’s announcement concerning autism treatments. Critics argue that the approval of leucovorin elevates an unproven drug that requires significantly more study before being recognized as a viable treatment for the complex neurological disorder.
Leading autism organizations and researchers quickly distanced themselves from the decision regarding leucovorin. They labeled the studies supporting its use as “very weak” and “very small.” David Mandell, a psychiatrist at the University of Pennsylvania, emphasized, “We have nothing resembling even moderate evidence that leucovorin is an effective treatment for autism symptoms.”
Mandell and other researchers assert that autism is primarily rooted in genetics, with additional contributing factors such as paternal age. Despite this, an increasing number of doctors are prescribing leucovorin, using formulations initially intended for chemotherapy or creating new versions through compounding pharmacies. While some researchers advocate for further studies on leucovorin, particularly for patients with folate deficiencies, they stress that it should only be administered in controlled clinical trials.
The rationale behind using leucovorin for autism stems from established science but quickly enters an area of uncertainty. When metabolized, leucovorin converts into folate, a vitamin crucial for healthy prenatal development. However, its impact post-birth is less understood. Interest in the potential link between folate levels and autism began over two decades ago when studies indicated that some individuals with autism exhibited low folate levels in the brain, potentially due to antibodies obstructing the vitamin's absorption.
However, the theory suggesting a connection between autism and folate levels was largely dismissed after research revealed that siblings of autistic individuals could also have low folate levels without showing symptoms. Mandell remarked, “I honestly thought this had died out as a theory for autism and was shocked to see its reemergence.”
In 2018, Dr. Frye and his colleagues published a study involving 48 children, where those administered leucovorin demonstrated improved performance on several language assessments compared to those on a placebo. Other small studies from countries including China and Iran yielded similar results, although they utilized different dosages and statistical methodologies, leading researchers to question the reliability of these findings. Dr. Frye faced challenges securing funding for continuing research within traditional academic frameworks, prompting him to innovate outside of academia.
Earlier this year, Dr. Frye and fellow researchers established the Autism Discovery Coalition to present their findings to Trump administration officials, including Health Secretary Robert F. Kennedy Jr. Following a meeting with National Institutes of Health Director Jay Bhattacharya, discussions with the Food and Drug Administration (FDA) about testing a proprietary version of leucovorin progressed. This new formulation would allow for patenting, potentially enabling Dr. Frye’s yet-to-be-formed drug company to charge significantly more than the currently available generics.
However, the FDA’s recent announcement may have jeopardized these plans. Instead of previewing a new formulation, the agency has opted to update the label on the existing generic drug to include its potential use for enhancing folate levels in the brain, including for autism patients. This change is anticipated to encourage more healthcare providers to prescribe leucovorin and may lead to broader insurance coverage.
Experts who have dedicated years to treating autistic patients emphasize the necessity of proceeding cautiously. Dr. Lawrence Gray, a pediatric developmental specialist at Northwestern University, recalls numerous experimental treatments that initially showed promise but ultimately failed in larger studies. “Small studies often find populations that are very motivated,” he noted. “But when those therapies are moved into larger studies, the initial positive findings often disappear.”
One of the significant challenges facing leucovorin is the lack of consensus regarding the percentage of autism patients who possess the folate-blocking antibodies that the drug allegedly targets. As the debate continues, the focus remains on ensuring that any treatments for autism are grounded in solid scientific evidence and rigorous testing.
