What is leucovorin, the drug Trump and RFK Jr claim can treat autism spectrum disorder?
Robert Kennedy Jr says the announcement opens "the door to the first FDA-recognised treatment pathway" for autism spectrum disorder, but not everyone is convinced. (Getty Images: Andrew Harnik)
In short:
The Trump administration has announced a drug called leucovorin (or folinic acid), currently used to treat the side effects of cancer drugs, will be made available to treat symptoms of autism in some children.
US health authorities say the approval of the drug is based on research that suggests it may help a subset of children who are folate-deficient improve their verbal communication.
What's next?
Health experts have warned that evidence of the benefits of leucovorin for autism is limited, and that larger studies are needed.
A prescription medicine used for patients with cancer and anaemia is set to be made available for the treatment of autism in some children in the United States.
On Monday, the Trump administration announced the US medicines regulator would be modifying the label — and expanding the use — of a drug called leucovorin, or folinic acid, a type of folate.
The update means leucovorin will be approved for the treatment of cerebral folate deficiency, which some doctors in the US had already been prescribing off-label for purposes not currently approved by the federal drugs regulator.
Cerebral folate deficiency, which the Trump administration says has been linked to autism, is a rare disorder that occurs when there are low folate levels in the brain despite normal levels in the rest of the body.
Children with cerebral folate deficiency usually develop symptoms from about the age of two, which are also seen in autism, including developmental delays and problems with movement.
Shortly after the White House announced leucovorin as a treatment for autism spectrum disorder, the Federal Drug Administration moved to approve the drug for that use. (Getty Images: Sarah Silbiger)
US Food and Drug Administration (FDA) officials said the expanded approval of leucovorin is based on research that suggests the drug may help children with autism who are folate-deficient improve their verbal communication.
"Children are suffering and deserve access to potential treatments that have shown promise," FDA Commissioner Marty Makary said.
According to US health authorities, leucovorin will be authorised for children with autism, "with continued use if children show language, social, or adaptive gains".
But Australian experts have warned that research into the drug and its potential benefits for autism was very preliminary, and have cautioned against its widespread use.
What is leucovorin?
Leucovorin, also known as calcium folinate and leucovorin calcium, is a type of vitamin B9, or folate.
Folate, which is naturally found in certain foods, helps the body make healthy red blood cells and is important for overall brain function.
While leucovorin is not the same as folic acid (the synthetic version of folate), the two substances are chemically similar. This means leucovorin, which is administered as pills or injections, can perform the same functions as folic acid.
Leucovorin is most commonly used to reduce side effects associated with some chemotherapy drugs and to treat some types of anaemia resulting from folic acid deficiency.
It can also enhance the effects of the chemotherapy drug 5-fluorouracil.
Side effects of the drug include fever, nausea, rashes and trouble sleeping.
Leucovorin is also approved by the Therapeutics Goods Administration in Australia for cancer treatment side effects and requires a prescription.
What is autism spectrum disorder?
Autism spectrum disorder (ASD), which includes autism and Asperger's syndrome, is a condition that affects a person's ability to interact with the world around them.
Autistic people can have difficulties with social communication and interaction, as well as restricted and repetitive behaviours.
Some research has suggested children with autism have genetic variations or autoimmune conditions that affect the body's ability to process folate or transport it to the brain. But, according to the Autism Science Foundation, these findings have been inconsistent.
What is the evidence for leucorvorin and autism?
In recent years, researchers have undertaken a handful of studies investigating leucovorin as a possible treatment for autism symptoms, and in some cases, they have found the drug may lead to improvements in behavioural and language outcomes.
One recent study in India, for example, compared 39 children on the medication and 38 on a placebo, and found those who took leucovorin had improved scores on the child autism rating scale. Other small studies in China, Iran and France have made similar findings.
But Andrew Whitehouse, a professor of autism research at The Kids Research Institute, said the overall evidence for leucovorin was "weak", and that studies to date were "limited by small numbers, inconsistent findings, and a lack of independent replication".
"Right now, the science does not come close to the standard needed to recommend leucovorin in the clinical management of autism."
When it comes to autism, Professor Whitehouse said leucovorin remained "experimental", and that large, rigorously controlled trials were needed to confirm whether any benefits were real.
"Current research is too narrow and preliminary to draw strong conclusions, and the enthusiasm far outstrips the scientific evidence."
Adam Guastella, a clinical psychologist from the Clinic for Autism and Neurodevelopment Research at the University of Sydney, agreed.
"There are some promising studies suggesting possible benefits, but these studies have many limitations," Professor Guastella said.
"They are not at the quality that is needed for widespread use."
In announcing the changes to leucovorin, US health authorities themselves noted that "while promising … leucovorin is not a cure for ASD and may only lead to improvements in speech-related deficits for a subset of children with ASD".
"Furthermore, this treatment must be administered under close medical supervision and in conjunction with other non-pharmacological approaches for children with ASD (for example, behavioural therapy)," the authorities said.
Professor Guastella added some research suggested leucovorin may have negative side effects.
"More work is needed to be certain about the correct dose and timing, particularly when given in pregnancy and early childhood, before being taken up as a treatment for the community."
What are the main causes of autism?
Autism is a complex neurodevelopmental disorder with no single known cause, said Hannah Kirk from the Turner Institute for Brain and Mental Health at Monash University.
"Research consistently shows that genetics play a large role — there are hundreds of genes that have been linked to autism," Dr Kirk said.
"There have also been some environmental factors that have been shown to have stronger associations, things like increased maternal age."
Loading...It's important to note that while folate is particularly important during pregnancy, and folic acid supplementation is recommended to help prevent birth defects, the link between maternal folate levels and autism is inconsistent.
Some studies have found mothers who took folic acid supplements around the time of conception had children with a significantly lower likelihood of autism, while other research has not observed the same association.
The Trump administration's advice, however, that pregnant women should limit their use of paracetamol because of links to autism in children, has been broadly condemned as "baseless" and causing unnecessary fear.
Can autism be treated?
Current treatments for autism are designed to reduce symptoms that impact "daily functioning and quality of life", Dr Kirk said.
"It's a complex disorder, so trying to find a simple answer [to what causes autism] is unlikely to be fruitful."
Clinical psychologist Dawn Adams added that the framing for leucovorin as a treatment for autism was "worrying" because such statements "impact how people understand and perceive autism".
"[Autism] is a neurodevelopmental difference," Professor Adams, from the Olga Tennison Autism Research Centre at La Trobe University, said.
"When we frame [autism] as a condition that needs 'fixing', we risk adding to the stigma autistic people already face.
"What really makes a difference for autistic people is the right supports: inclusive classrooms, workplaces that adapt to needs, communities that understand communication and sensory differences, and policies shaped by good-quality research," she said.
Professor Whitehouse said there were already "many support programs with strong scientific backing that reliably support development in autistic children".
Other Australian researchers also encouraged people with autism to continue to follow evidence-based best practice and said that the Australian government should not change its leucovorin prescribing guidelines.