Leucovorin: What to know about the drug newly approved for autism treatment

This week, the Food and Drug Administration announced that leucovorin, an unobtrusive drug that has been used for decades in treating cancer, will bear a label stating that it may be of benefit in treating autism. FDA Commissioner Dr. Marty Makary said the action will make the drug "available for children with autism," the first time that the agency has approved such a use, the New York Times reported.

What is leucovorin

Leucovorin, or folinic acid, is a chemically altered form of vitamin B9, or folate. Also occurring naturally in green leafy vegetables, beans, citrus fruits, eggs, and beets, folate plays the key role in red blood cell formation as well as in normal cell growth. During pregnancy, folate prevents severe brain and spinal defects in infants. Since then, scientists have speculated that folate also plays a role in depression, dementia, heart disease, and autism.

Why autism researchers are interested

There are a few reports that as many as three-quarters of people with autism will have antibodies against folate transport in the body. This has been called cerebral folate deficiency and can limit folate from entering the brain. Symptoms usually appear at around age two and may include speech impairment, seizures, intellectual disability, tremor, and difficulty with muscle coordination. Leucovorin is designed to circumvent these blocks, enabling brain folate to become normal and for symptoms to improve.

The evidence thus far

The FDA decision is based on research conducted between 2009 and 2024. In one study, 80 children were administered either leucovorin or a placebo, and children who received leucovorin had "substantial improvement" in their symptoms, versus the placebo group. In Dr. Richard Frye's research, some of the children who were administered folinic acid had better receptive and expressive language skills, allowing them to comprehend and communicate more clearly. But the effects have been inconsistent — the majority of the children in these studies experienced little or no relief.

Not a cure, but a possible assistant

Leucovorin is not a cure for autism, experts say. "It improves the function of many children markedly, but it is not a cure," Dr. Frye said. Researchers on autism such as Dr. Alycia Halladay of the Autism Science Foundation say larger placebo-controlled trials are still needed to determine which patients will see improvement and at what doses. They point out that autism remains a complex disorder with both genetic and environmental factors, so that the possibility of a single treatment alleviating everyone is doubtful.

Other uses approved

Until now, leucovorin has only been used to reduce the toxicity of monotherapy drugs such as methotrexate, and with fluorouracil to treat colorectal cancer. It is also used for megaloblastic anemia, a disorder caused by a deficiency of folic acid. The drug is available in pill, injectable, or intravenous solution form, and can be compounded into a liquid as well. Insured compounding forms are commonly limited, creating another barrier to families.

Side effects and safety

Because leucovorin is derived from a water-soluble vitamin, most of it is eliminated from the body in urine within 24 hours and therefore limits its risk. Side effects documented are very mild and include headaches, insomnia, agitation, irritability, and tantrums in some children. Researchers pen that in general, the drug is safe, but more data is needed to confirm its long-term impact on autistic children.

Looking ahead

For parents of autistic children, the FDA decision is one of cautious optimism. Already some families were experimenting with leucovorin off-label. Now, they have official acceptance that in certain instances, the drug is useful. But experts are warning against hasty assumptions about the medicine being a cure-all. With scant funds being directed toward research on autism, some argue that it might be better spent on therapies with stronger evidence. For now, leucovorin is a hopeful though unfinished answer to the larger war to treat children on the spectrum.