FDA Initiates Approval of Leucovorin for Autism Symptoms

• Leucovorin is a form of folate that can reach the brain more effectively than regular folic acid.
• Studies show leucovorin may improve speech, behavior, and social interaction in children with autism who have cerebral folate deficiency.
• Children with folate receptor antibodies tend to respond best to leucovorin treatment, especially in verbal communication.
• The FDA is moving toward approval of leucovorin for CFD, offering families a regulated treatment option backed by clinical research.

On September 22, the U.S. Food and Drug Administration announced that it is initiating approval of leucovorin calcium tablets for patients with cerebral folate deficiency (CFD), a condition linked to developmental delays and autistic features.

What is Cerebral Folate Deficiency?

Cerebral folate deficiency (CFD) is a condition that can affect how a child’s brain grows and develops. It happens when the brain doesn’t get enough of a specific form of vitamin B9, called 5-methyltetrahydrofolate.

Folate is like a building block that helps the brain work properly, especially in young children as they grow. When folate levels in the brain are too low, it can lead to developmental challenges.

This condition often starts to show signs around age 2, when children are rapidly developing skills like talking, socializing, and moving. If not addressed, CFD can cause delays in these areas and, in some cases, other symptoms like seizures or trouble with movement.

How Does Folate Get to the Brain?

Folate needs to reach the brain to do its job. A special protein called folate receptor alpha acts like a delivery system, carrying folate from the blood into the brain. If this delivery system doesn’t work properly, the brain may not get enough folate, even if there’s plenty of folate in the blood. This can happen for different reasons, including when the body produces antibodies that block the folate receptor alpha from working correctly.

The Link to Autism

Recent research has found a strong connection between CFD and certain developmental conditions, particularly autism spectrum disorder (ASD).

In many children with autism, their body creates special proteins (antibodies) that mistakenly attack the folate receptor alpha. This is similar to how a key might get gummed up and no longer work in the lock. These antibodies block the folate from getting into the brain, causing a shortage.

Studies have shown that a high percentage of children with autism have these antibodies, while they are much less common in children without autism.

What is Leucovorin?

Leucovorin (folinic acid) is a prescription medication that provides a form of folate (vitamin B9) the body can use right away. While similar to folic acid, leucovorin is not exactly the same, it is more effective for certain medical conditions, especially when the brain has trouble getting enough folate.

Leucovorin is already approved by the FDA for several uses:

• Reducing side effects from certain chemotherapy drugs
• Supporting cancer treatments
• Treating specific types of anemia caused by low folate levels

Now, researchers are exploring how leucovorin can help children with CFD, a condition where low folate levels in the brain can lead to developmental delays and autism-related symptoms.

Why is Leucovorin Being Studied for CFD?

In CFD, the brain doesn’t get enough folate because of problems with a protein that transports folate into the brain. Leucovorin is being studied because it can provide the brain with the folate it needs, bypassing some of these delivery issues.

Doctors have used leucovorin “off-label” for years in children with CFD, and many families have noticed improvement in communication, movement, and behavior.

What Do Studies Show About Leucovorin and CFD?

Several studies have explored how leucovorin can help children with CFD, and the results are encouraging.

• Improved Symptoms: In a study of 80 children, half received leucovorin, and half received a placebo. The children taking leucovorin showed significant improvements in CFD symptoms compared to those who got the placebo.
• Better Verbal Communication: Another study found that leucovorin helped children improve their ability to speak and communicate. The biggest improvements were seen in children who had antibodies blocking folate transport, suggesting leucovorin may work especially well for them.
• Gains in Autism Symptoms: A more recent study followed children for 24 weeks. Those who took leucovorin showed improvements in their overall autism-related symptoms, like social challenges and repetitive behaviors. Children with higher levels of folate-blocking antibodies saw even greater benefits.

What Does This Mean for Families?

Based on years of this kind of evidence, the FDA is moving forward with official approval of leucovorin for treating CFD. While more research is still needed, this decision is a huge step forward. It means that doctors and families will have a clear, regulated way to consider using leucovorin to help manage symptoms related to this condition.

While experts agree that more research is needed, this move makes it easier for families and doctors to access leucovorin within a clear regulatory setup—helping families know what to expect and providing safer, more reliable care.

Speak with Your Doctor

The FDA’s recent decision doesn’t mean leucovorin is approved to treat autism, and it’s not a cure. What it does mean is that research has shown some kids with CFD and autism features may see improvements in things like language and communication when they take it.

It’s also important to know that the data we have so far is limited. The FDA emphasized that further studies are still necessary to fully understand the effectiveness of leucovorin in this group and its long-term safety.

If you’re wondering whether leucovorin could be an option, talk to your doctor first. Every child’s case is different, and your provider can explain whether this medication is appropriate for you.