Explained: Why US Is Considering Leucovorin For Autism Treatment

US Food and Drug Administration publishes notice approving GlaxoSmithKline's version of leucovorin for potential autism treatment

Medical professionals have been utilizing leucovorin as an off-label prescription for autism patients.

On Monday, the FDA officially published a notice in the Federal Register, preceding an address by President Donald Trump, giving approval to a leucovorin formulation manufactured by GlaxoSmithKline. This particular version had previously been withdrawn from FDA consideration when the company discontinued its production.

The FDA's decision referenced a review examining leucovorin's effects in 40 patients diagnosed with cerebral folate deficiency, a rare metabolic disorder causing various neurological symptoms that sometimes overlap with those observed in autism cases.

Below is essential information about leucovorin and its relationship to autism treatment.

Understanding Leucovorin

Leucovorin, alternatively called folinic acid, represents a form of folate, which is classified as vitamin B9, an essential nutrient.

The US Food and Drug Administration has approved leucovorin primarily for counteracting toxic effects of certain cancer medications, particularly methotrexate, which inhibits the body's folate utilization processes.

Additionally, leucovorin serves to enhance efficacy of other chemotherapy drugs and treats specific anemia types. Administration can occur either orally or through intravenous methods.

According to the FDA website, over half a dozen pharmaceutical companies currently manufacture this medication.

The Significance of Folate

Folate plays crucial roles in cell growth and division processes. It additionally supports immune system function and contributes to healthy red blood cell production. During fetal development, insufficient folate can lead to serious neural tube defects.

The US Centers for Disease Control and Prevention recommends that all women with childbearing potential supplement their diet with 400 micrograms of folic acid daily to help prevent neural tube defects.

Some research studies, though not unanimously, have identified associations between low maternal folate levels during early pregnancy and increased autism risk in offspring.

Rationale for Leucovorin in Autism Treatment

Physicians have been prescribing leucovorin for autism through off-label use—the practice of repurposing medications approved for one condition to address another.

Research from SUNY Downstate Medical Center in Brooklyn, New York, and other institutions suggests that approximately three-quarters of children with autism possess genetic variations impairing folate processing or have autoimmune disorders blocking folate transport to the brain.

Additional small-scale studies have connected these findings with more severe manifestations of autism and indicated that leucovorin treatment might improve verbal abilities, social skills, and reduce irritability in affected children.

Nevertheless, the Autism Science Foundation emphasized in a statement that scientific understanding regarding leucovorin and autism "is still in very early stages, and more studies are necessary before a definitive conclusion can be reached."

The foundation notes on its website that supporting evidence for leucovorin treatment comes from "four small randomized controlled trials, all using different doses and different outcomes, and in one case, reliant on a specific genetic variant."

Dr. David Mandell, psychiatry professor and autism specialist at the University of Pennsylvania, told Reuters that while leucovorin might potentially benefit some children with autism, "the evidence we have supporting it... is really, really weak."