The condition targeted in the FDA approval is a genetic version of cerebral folate deficiency, caused by mutations in a folate receptor gene. People with CFD — whether from genetic or other causes — have low levels of folate in their cerebrospinal fluid, which leads to reduced folate in the brain. This affects brain development. Patients with genetic CFD can experience developmental delays, movement disorders and seizures. Some behaviors are similar to those of people with autism.
However, this form of genetic CFD is estimated to occur in 1 in a million people, according to the FDA. That would translate to around 70 kids in the U.S. — far from “hundreds of thousands of kids.” Leucovorin had already been used for decades to treat genetic CFD via off-label prescribing, a common practice when evidence shows a drug approved for one condition improves another.
This was the same press conference in which President Donald Trump and others touted an unproven link between autism and the use of Tylenol, or acetaminophen, during pregnancy.
Makary later referred to a subset of people with autism with antibodies that block their own folate receptors, called autoantibodies. Some researchers have hypothesized that a subset of people with autism have CFD caused by these autoantibodies, but this is not well-established, as we will explain.
