I’m the doctor on the cusp of an autism breakthrough… we’re using an everyday drug to reverse children’s symptoms

Parents of autistic children see Dr Richard Frye as a ‘miracle’ worker, and it’s not hard to understand why.

Told that their youngsters might never utter a word, they describe the absolute joy of hearing them say ‘mom,’ ‘dad,’ or ‘I love you’ for the first time.

But Dr Frye would disagree with their assessment of him. He’s performing no miracles. 

Instead, he’s working to better understand the workings of a drug he believes is modern medicine’s best kept secret and building on solid research with one goal – a breakthrough in treating autism and perhaps even preventing it in the first place.

In his Arizona clinic, dozens of previously nonverbal youngsters have been helped to speak their first words. In some of these cases, they are talking in complete sentences and using a wide vocabulary in just a few months.

Dr Frye, a pediatric neurologist at Rossignol Medical Center in Arizona, has been achieving these remarkable results using leucovorin.

A cheap medication – just $2.50 per pill – it 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.

Women are already advised to take folic acid during pregnancy to prevent birth defects in the fetal brain and spinal cord, but Dr Frye believes the benefits extend well beyond gestation.

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

Research suggests up to three in four autistic children don’t get enough folate supply to their brain, causing delays in speech and behavioral issues.

Leucovorin is approved in the US for patients to protect their cells – especially blood cells – against the damaging effects of chemotherapy, but doctors can prescribe it ‘off label’ for other conditions since it has been deemed safe by the FDA.

Dr Frye is one of just 50 doctors in the US prescribing it because it is not yet approved for autism. He believes dozens of his patients have seen ‘substantial improvements’.

One of those patients is Mason Conner, who said his first words just three days after starting daily leucovorin. Diagnosed with autism at age two and a half, and once completely nonverbal, he will start mainstream kindergarten next fall.

Dr Frye’s team is now testing a new form leucovorin that could be FDA approved within three to five years, not only for autistic children but also for people with Down Syndrome, schizophrenia, and dementias who may also be deficient in folate.

Dr Frye is looking into screening tests for folate deficiency in utero or even before pregnancy ‘so we can understand what the folate needs may be and actually prevent autism from occurring in the first place’.

Leucovorin would also be far cheaper than standard therapies like applied behavior analysis (ABA), which can cost up to $250,000 per year without insurance and involve up to 40 hours a week of intensive therapy.

Dr Frye cautioned that many autistic patients would still need standard therapies on top of the leucovorin. But he claimed drug may reduce the amount of therapy necessary.

He told DailyMail.com: ‘[Leucovorin] can supercharge all their therapies and get them on the road to success.’

Other experts agree that while this research ‘appears to hold real promise’, leucovorin is still ‘unproven and experimental’.

There is certainly a desperate need for new approaches in managing autism. The number of children diagnosed with the condition is on the rise in the US, going from seven in 1,000 in the early 2000s to one in 36 in 2022 – just under two million in total.

So how is leucovorin believed to help? 

Research on the drug dates back to the early 2000s, during which scientists Dr Vincent Ramaekers of 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 of antibody that mistakenly targets and attacks the body’s tissues and organs.

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.

Dr Frye said: ‘Folate is extremely important, especially in growing cells.’

He explained that folate 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 folate.

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

Following Dr Ramaekers’ and Dr Quadros’ research, Dr Frye’s team started testing children at their clinic for the autoantibody using spinal fluid samples.

Dr Frye said: ‘If they had the autoantibody, we offered them treatment with leucovorin.’

He explained that unlike other forms of folate, such as those in vitamin supplements, leucovorin is a ‘special form’ of folate that can 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.

In a recent trial, researchers found that after four months on leucovorin, autistic children on the medication ‘had significant improvements in language, particularly verbal communication, expressive language, and receptive language’.

Now, Dr Frye’s team is testing a new form of the drug called L-leucovorin, which comes in a liquid, tasteless form specifically geared toward autistic children, many of whom struggle with sensitivity to certain textures, tastes, and colors.

Dr Frye estimates the latest trial will have results by summer, and data so far ‘looks very promising’.

He cautioned that it could be up to five years before leucovorin is FDA approved for autism.

The FDA told his team it would need to conduct at least one more large study – called a dose-finding trial – to determine the appropriate dose before leucovorin approval could be sought.

FDA approval could, of course, make the treatment more widespread.

In Dr Frye’s clinic, one in five patients – about 2,000 – take leucovorin. It’s unclear what side effects could come with L-leucovorin, but standard leucovorin can lead to dizziness, seizures, shortness of breath, fatigue, hives, diarrhea, vomiting, and itching, according to the Cleveland Clinic in Ohio.

The team is also investigating if drugs like leucovorin could lead to improvements in other developmental and psychiatric disorders.

Dr Frye pointed to pediatric acute onset neuropsychiatric syndrome (PANS), a condition that causes children to develop sudden psychiatric symptoms like anxiety, irritability, and signs of obsessive-compulsive disorder.

He estimates about 60 percent of the one in 11,000 children with PANS are deficient in cerebral folate.

Children with Down Syndrome are also at an increased risk of cerebral folate deficiency, and early research suggests people with dementia and schizophrenia may be as well.

Dr Frye said: ‘We think there’s a wide number of neurological and psychiatric disorders that may respond to the same treatment.

‘It’s not going to be everyone, but even if it’s a small percent, that you can really find something that eliminates their symptoms without side effects, I think it’s a real win.’

Dr Brandon Crawford, a developmental functional neurologist at the Neurosolution Center of Austin, is more cautious. He says he has seen ‘mixed results’ with leucovorin.

He said: ‘While the emerging research is promising, it is important to recognize that autism and other neurobehavioral disorders are typically multifactorial conditions that require a comprehensive, multimodal approach to care.

‘Leucovorin may be a valuable option for certain individuals, particularly those with documented folate metabolism issues, but it is not a universal solution.’

Thomas Freeman, an applied behavioral analyst and senior vice president at ABA Technologies in Florida, told DailyMail.com that ‘Leucovorin appears to hold real promise in this area.’

However, he said that the research is still early, and autistic children often still need additional therapies.

‘The public should see this story as a hopeful sign of a possible new therapeutic intervention but should temper that view of this treatment as being so far unproven and therefore experimental only,’ Freeman added.

Freeman said the ‘strongest evidence-based approach’ to treating autism is applied behavior analysis (ABA) therapy, which uses positive reinforcement and repetition to help children on the autism spectrum develop behaviorally.

And Dr Ozan Toy, a psychiatrist and Chief Medical Officer at Telapsychiatry, said that ‘leucovorin significantly improves communication’ and ‘has a positive effect on core ASD symptoms and associated behaviors’ like inattention and repetitive behaviors, also called stimming.

‘I would still advise parents to utilize all educational, speech and occupational therapies for your child and not neglect these resources while taking leucovorin,’ he said.

Dr Frye agreed that for many autistic children, leucovorin alone is likely not enough on its own to help them speak for the first time.

Instead, it’s one part of the puzzle.

Dr Frye said: ‘The truth about kiddos with autism is it’s not a simple disorder. It’s just not one fix, and there’s no ‘autism pill.’ Unless you have good therapy, good speech therapy, good behavioral therapy, leucovorin isn’t going to work all that well.

‘It will help the brain repair itself and give the brain what it needs, but these children have to catch up in development. They need that educational support to get their brain back to where it should be.’