Why is leucovorin being considered as an autism treatment?

On Monday, the U.S. Food and Drug Administration published a notice to the Federal Register ahead of a speech by President Donald Trump, approving a version of leucovorin made by GlaxoSmithKline that the company had previously withdrawn from the FDA's consideration when it stopped manufacturing the drug.

The FDA cited a review of the use of leucovorin in 40 patients with a rare metabolic disorder called cerebral folate deficiency that can lead to a range of neurological symptoms, some of which are seen in people with autism.

Here's what is known about leucovorin and autism.


WHAT IS LEUCOVORIN?

Leucovorin, also known as folinic acid, is a form of folate, an essential B vitamin, or B9.

Leucovorin has been approved by the U.S. Food and Drug Administration for counteracting the toxic effects of certain cancer drugs, like methotrexate, that block the body's use of folate.

Leucovorin is also used to enhance the effects of other chemotherapy drugs and to treat specific types of anemia. The drug can be given orally or intravenously.

It is made by more than half a dozen companies, according to the U.S. Food and Drug Administration website.

WHY IS FOLATE IMPORTANT?

Folate helps cells grow and divide. It also supports the immune system and helps produce healthy red blood cells. In developing fetuses, inadequate folate leads to a type of serious birth defect called neural tube defects.

The U.S. Centers for Disease Control and Prevention advises all women capable of becoming pregnant to supplement their diet with 400 mcg of folic acid every day to help prevent neural tube defects.

Some studies, but not all, have also found an association of low maternal folate levels during early pregnancy with an increased risk of autism in children.

WHY CONSIDER USING LEUCOVORIN TO TREAT AUTISM?

Doctors have been prescribing leucovorin for autism off-label, or repurposing a drug approved for one condition to treat another.

Studies from researchers at SUNY Downstate Medical Center in Brooklyn, New York, and elsewhere have suggested that up to three-fourths of children with autism have genetic variations that impair their body's ability to process folate or autoimmune disorders that block folate transport to the brain.

Other small studies have linked these findings with more severe forms of the disorder and suggested that treatment with leucovorin can improve verbal skills, social skills and irritability in these youngsters.

However, the science regarding leucovorin and autism "is still in very early stages, and more studies are necessary before a definitive conclusion can be reached," the Autism Science Foundation said in a statement.

The data in favor of treatment with leucovorin is "from four small randomized controlled trials, all using different doses and different outcomes, and in one case, reliant on a specific genetic variant," the Foundation notes on its website.

Dr. David Mandell, a professor of psychiatry and autism expert at the University of Pennsylvania, told Reuters that leucovorin might well be a possible treatment for some children with autism, "but the evidence we have supporting it... is really, really weak."