New Delhi: The U.S. Food and Drug Administration (FDA) has recently approved the use of leucovorin, a drug derived from folic acid, in the treatment of cerebral folate deficiency (CFD), a rare metabolic disorder that can trigger neurological symptoms often resembling those seen in autism. The announcement, published in the Federal Register, coincided with remarks that former U.S. President Donald Trump was expected to make about potential treatments for autism.
Leucovorin, popularly known as folinic acid, is a form of folate that helps cells divide, grow, and function properly. It is also known as vitamin B-9, which helps produce healthy red blood cells and supports immune health as well. During pregnancy, folate is a must for a mother-to-be as its insufficient levels can result in birth defects like neural tube abnormalities. Therefore, the CDC recommends women of childbearing age take folic acid supplements every day.
Conventionally, leucovorin was used for several purposes, often prescribed along with chemotherapy drugs to mitigate side effects. It is also effective for cancer therapies and to treat some forms of anaemia. The drug is available for oral and intravenous use. But what is most noticeable is that it has a potential link to autism-like symptoms. Although the drug is not officially recognised as an autism treatment, it can sometimes be accompanied by behavioural and developmental problems resembling autism traits. According to the FDA, data from around 40 patients, both adults and children, indicated that leucovorin improved symptoms related to CFD.
The story of leucovorin is not new. GlaxoSmithKline (GSK) once marketed the drug under the brand name Wellcovorin but withdrew it in 1997 for business reasons unrelated to safety or efficacy. However, the company retained its New Drug Application (NDA), which allowed it to reintroduce the drug at the FDA’s request. GSK has now agreed to update the product’s label to reflect its use for CFD treatment.
Why does this matter for families affected by autism? Over the past decade, some doctors have prescribed leucovorin “off-label” for children with autism. Research from SUNY Downstate Medical Center and other institutions suggests that up to 75% of children with autism may have genetic or autoimmune problems that disrupt folate metabolism or block folate transport into the brain. In these cases, leucovorin supplementation has shown promise in improving language, social engagement, and reducing irritability.
Yet, experts warrant caution – the Autism Science Foundation noted that evidence is limited and has been gathered from only four small clinical trials that used varied methods and had inconsistent outcomes. Dr. David Mandell, an autism researcher at the University of Pennsylvania, has also noted that while leucovorin may eventually prove useful for some children, the current scientific support is “really, really weak.”
For now, leucovorin’s official approval is limited to treating CFD, not autism. But its renewed availability may encourage larger, more rigorous studies that could clarify its role in addressing autism-related symptoms in the future.