In a Sept. 22 press conference, the Trump Administration introduced what it says is an “exciting treatment” for autism: leucovorin, a decades-old medicine that treats toxic effects of chemotherapy. Early research suggests it can be helpful for a certain group of people with a neurological condition related to autism, though some medical experts say it’s not quite ready to be used as widely as the administration plans.
Here’s what to know about leucovorin.
What is leucovorin?
Leucovorin is a form of folic acid, which is a synthetic form of folate (vitamin B9). Folic acid is important for helping the body make DNA and red blood cells, hair and nail cells, skin cells, and others throughout the body. The American College of Obstetricians and Gynecologists recommends that all women who are pregnant or planning to get pregnant take a daily folic acid supplement to avoid neural tube and spinal defects in developing fetuses. Folic acid is also important for preventing certain types of anemia.
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Certain childhood and adult cancers are treated with methotrexate, a type of chemotherapy that can cause toxic effects on the body, particularly for the kidneys, by interfering with normal folate activity in cells. Leucovorin, or folinic acid, can counteract those effects by substituting for folate and allowing the body’s folate processes to continue functioning in the presence of methotrexate.
What does leucovorin have to do with autism?
In recent years, scientists have reported that some children with autism have lower levels of folate in their brains, even while having normal levels of folate in the rest of their body. The deficiency can be traced to several factors, says Dr. Richard Frye, chief scientific officer of the Autism Discovery and Treatment Foundation and director of research at Rossignol Medical Center, who has studied the connection between folate and neurological disorders for decades.
In some cases, people with lower brain folate levels may have antibodies that bind to the folate receptors in the brain, blocking the ability of folate to function in the brain. In 2005, researchers in the U.S. and Europe published a study linking these antibodies with cerebral folate deficiency (CFD), a rare condition in which people have low levels of folate in the brain, which leads to certain neurological symptoms including slow psychomotor and head growth, irritability, involuntary or repetitive movements, and seizures. In that small study, folinic acid improved the children’s symptoms.
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Other people with low brain folate levels have abnormal mitochondria, which regulate energy in cells, and that impairs the cells’ ability to obtain folate. Some people also have genetic defects that produce faulty folate receptors.
In 2013, Frye published a small study showing that children with autism as well as those with CFD could benefit from leucovorin. In his study, up to 75% of children with autism showed deficiencies in brain folate, and that children with lower levels of the folate receptor in particular improved their language, interpersonal, social, and coping skills. Five years later, Frye confirmed those findings in a study that compared children receiving leucovorin to a group getting a placebo drug.
“I think [leucovorin] is a major step forward to get many children treated and improve their ability to function,” he tells TIME. “It is particularly groundbreaking in the fact that many do not think that autism can be treated at its core. This treatment fixes core biological deficits and therefore could be disease-modifying. It is not a cure, but can improve the function of many children substantially.”
Dr. Marty Makary, commissioner of the U.S. Food and Drug Administration (FDA), said during the press conference that the agency had begun the process to approve the drug, which is now generic, to treat people with autism. However, the official FDA statement said the drug’s approval would be for people with CFD. While CFD can lead to autism-like symptoms and developmental delays, it is distinct from autism. Many people with CFD have autism, but not all people with autism have CFD.
How can you tell if someone with autism has low folate levels in the brain?
Doctors can test for folate levels in the brain with a lumbar puncture (also known as a spinal tap) to detect folate levels in the cerebrospinal fluid. They can also test for the antibodies against folate in the blood through a folate receptor autoantibody test (FRAT), which is not part of routine blood work.
Is leucovorin approved to treat autism?
The drug is only approved to treat the effects of chemotherapy. But with the FDA’s latest action, doctors can prescribe it for CFD. “Autism may also be due to an autoimmune reaction to a folate receptor on the brain not allowing that important vitamin to get into the brain cells,” Makary said during the press conference. “We have a duty to let doctors and the public know we are going to change the label to make it available. Hundreds of thousands of kids, in my opinion, will benefit.”
The branded version of the drug, made by GSK, was originally released in the early 1980s, but the company stopped marketing it in 1999, and the FDA withdrew approval. Generic versions have since emerged, and some doctors began prescribing it off label for autism patients. The FDA is now working with GSK to re-introduce the drug with its new indication for CFD.
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Frye believes the data so far support prescribing leucovorin for autism, especially since there are so few treatments. “I personally wouldn’t consider it experimental,” he says. “I would prescribe it as a treatment that has good evidence as effective.” He says that the drug shouldn’t be a first-line treatment, but should come after interventions like speech and occupational therapy, and after behavioral and sleep and gut issues are addressed.
Frye says he is working on creating a company to develop a version of leucovorin that is more appropriate for children with autism—an oral form that is colorless, tasteless, and odorless and could be given in a liquid, since some children may struggle with taking pills.
Is there really enough evidence that leucovorin works for autism?
Not everyone in the field has the same confidence in the data. Alycia Halladay, chief science officer at the Autism Research Foundation, says leucovorin is not yet ready to become a treatment for autism. “I think it’s incredibly premature to say leucovorin is anything more than a potential idea that has yet to get any real scientific data,” she says. “Most autism experts I know would not prescribe leucovorin and would not advise [families] to take it.”
Halladay says there is not enough safety data on the drug in children—much less children with autism, who may have additional medical issues—and some anecdotal reports find that leucovorin can make some children with autism more hyperactive. “The reality is that we don’t have the safety data yet. We need larger studies.” Another unknown is how long kids would need to take the drug, since no long term studies have been conducted. (Frye says that “for kids that do respond, it does seem like a long-term treatment.”)
Halladay also notes that the new attention on leucovorin may divert already limited resources, like research funding and support for clinical trials, away from more robustly studied strategies for autism, such as behavioral interventions or other drug approaches, that may have stronger scientific support.
The American Academy of Pediatrics (AAP) expressed similar concern about the dangers of oversimplifying treatment. “Regarding autism, we know it is complex, highly variable and increasingly linked to genetics. There is no single root cause of autism, and there is no single medication that will give every autistic child or adult what they need,” said AAP president Dr. Susan Kressly in a statement. “Individualized plans, often involving a combination of developmental, behavioral, educational, and social-relational strategies, can help improve outcomes that are meaningful to individuals and families.”
While Halladay welcomes the attention that the government’s announcements have on highlighting the need to better understand and treat autism, she cautions that not all attention is beneficial. “The increased spotlight on autism and the needs of people with autism is very helpful,” she says. “But using the platform to talk about things that don’t work, or could be harmful or potentially create a lack of trust in science, is not a good thing.”
The post What to Know About Leucovorin, an Old Drug Rebranded as an Autism Treatment appeared first on TIME.
