Medical professionals are raising concerns about a low-cost drug being expedited as a treatment for certain autism symptoms.

The American Academy of Pediatrics (AAP), a prominent organization representing pediatricians in the U.S., announced on Friday that it does not support the regular use of leucovorin for children with autism.

This medication, priced at $2.50 per tablet, is derived from folic acid, a nutrient commonly prescribed to pregnant women to aid in the proper neurological development of their unborn children.

Originally utilized since the 1950s to protect cancer patients’ cells from the harmful effects of chemotherapy, leucovorin is also being used off-label for children with autism.

Research has indicated that it can enhance language pathways in the brain, enabling previously non-verbal children to begin speaking when taken daily.

However, the AAP has cautioned against its regular use, citing ‘very limited evidence’ that the benefits of leucovorin outweigh potential risks and highlighting the lack of clear guidance on appropriate dosages for children.

However, neurologists who have studied leucovorin’s effects in autistic children told the Daily Mail that the ‘fact is quite the opposite’ and that leucovorin ‘is one of the safest drugs available’ compared to other medications given to autistic children, such as antipsychotics, which carry a long list of potential side effects. 

The debate comes as the FDA is in the process of approving leucovorin for children and adults with cerebral folate deficiency (CFD), which occurs when the brain can’t absorb folate, a naturally occurring form of folic acid found in foods like leafy greens.

The American Academy of Pediatrics warned against routine use of leucovorin, which has been shown to improve speech in children with autism, over ‘very limited evidence’ (file photo)

Recent research shows about three in four autistic people have CFD, which could be the culprit behind speech and behavioral issues seen in many cases of autism. 

The approval could take several years if the FDA requires additional safety trials, but endorsement of the medication from health officials within the Trump administration at a press conference last month has led to increased interest and demand. 

Dr Kristin Sohl, an autism expert at the University of Missouri who worked on AAP’s guidance, told Reuters there is ‘very limited evidence’ for leucovorin’s use in autism. 

She said: ‘We don’t know who this medicine is supposed to work for. We don’t know whether it’s safe. We don’t know what dose to start with. 

‘If this is something that can be supportive of an autistic child’s developmental progress, then great, but we also don’t want to just throw things at someone because we don’t know what else to do.’ 

Dr Sohl said she has faced increased demand in her practice for leucovorin but has only prescribed it once. 

Leucovorin is derived from folic acid (also known as Vitamin B9), a vital nutrient that helps synthesize DNA and replicates and repairs cells throughout the body. 

Its naturally occurring form, folate, is found in foods such as leafy green vegetables, beans and lentils.

Folic acid is a precursor to DNA and RNA, which are needed to help replicate a cell’s genome – a set of instructions that help cells function properly. This is why most prenatal vitamins contain folic acid.

Research on leucovorin dates back to the early 2000s, during which scientists Dr Vincent Ramaekers of the University of Liege in Belgium and Dr Edward Quadros of SUNY Downstate University of New York, took blood and spinal fluid samples from autistic children and found that while they had normal folic acid levels in their blood, there was much less in their cerebrospinal fluid, which protects the brain and spinal cord.

This suggested that something was blocking folate’s absorption by the brain.

The researchers also found 75 percent of autistic children had autoantibodies in their blood, a type that mistakenly targets and attacks the body’s tissues and organs.

Nathaniel Schumann (left), 12, would only speak two to three words at a time before starting leucovorin. Now, he can speak in full sentences. And 10-year-old Meghan Dumesnil (right) has seen ‘dramatic’ speech improvements since starting the drug

These autoantibodies are known to block a protein called folate receptor alpha, a protein that transports folic acid from the blood into the brain and placenta.

Research suggests that leucovorin may clear chemical blockages in the brains of autistic children, and this contributes to improving their language skills

But unlike other forms of folate, such as those in vitamin supplements, leucovorin is able to cross the blood-brain barrier – a semi-permeable layer lining the inner surface of blood vessels in the brain that protects it from potentially damaging substances in the blood. 

This means it can penetrate the brain and have a direct effect.

The FDA’s move to approve leucovorin is based on an analysis of data from about 40 cases, showing improvements in behaviors such as speech in autistic children taking leucovorin. 

Dr Richard Frye, a pediatric neurologist at Rossignol Medical Center in Arizona, has seen non-verbal children begin speaking in full sentences in a matter of weeks on leucovorin, as well as display less aggression and anxiety. 

Dr Richard Frye, a pediatric neurologist at Rossignol Medical Center in Arizona, told the Daily Mail that leucovorin ‘is one of the safest drugs available’ for autistic children

Daily Mail previously spoke with the parents of several children treated by Dr Frye who were prescribed leucovorin. One boy from Missouri was almost completely non-verbal before taking leucovorin. After two weeks, he told his father he loved him for the first time.

Another 12-year-old boy went from only speaking one or two works at a time to being able to tell his family in full sentences what was bothering him about six weeks after starting one of Dr Frye’s trials on leucovorin. 

Dr Frye told the Daily Mail in response to AAP’s announcement that ‘the fact is quite the opposite’ about leucovorin. 

‘Leucovorin is one of the safest drugs available,’ he said. ‘Leucovorin was approved for use to protect the body from chemotherapy side effects in the 50s. Thus, we have over 70 years of experience in regards to its safety.’

He noted that because folate in leucovorin is water soluble, excess levels are excreted out of the body through urine, ‘the body’s natural safety mechanism’, and synthetic folate like this does not have an upper safety limit. 

Autism experts told the Daily Mail that while leucovorin is safe and effective, it is not a cure for autism, and children with the condition typically need additional therapies (stock image) 

He compared this to other medications used for autism, risperidone (Risperdal) and aripiprazole (Abilify), which are both antipsychotics. 

‘These are known to cause weight gain, diabetes and tardive dyskinesia [a neurological disorder that causes involuntary face and jaw movements],’ Dr Frye said. 

In addition to the 40 case studies cited by the FDA, Dr Frye also pointed toward five involving more than 250 children, which ‘is comparable to the number of children used in the registration studies to gain FDA approval for the currently approved medication for autism’.

‘In conclusion, leucovorin is much safer than the current medications approved for autism and more effective,’ he added.  

But he has emphasized that leucovorin is not a cure for autism, and it often needs to be used alongside other therapies and medications such as risperidone and aripiprazole.