November 07, 2016
Expert Q&A: Richard Frye, MD, PhD
Children with autism often have trouble communicating with those around them. To gain social acceptance, they’re currently limited to enduring hours of weekly behavioral therapy and taking antipsychotic medications that typically do more harm than good. But new research offers hope of breaking down the communication barriers that prevent autistic kids from interacting with friends, family, and loved ones.
Dr. Richard Frye, a pediatric neurologist and director of autism research at Arkansas Children’s Hospital, led a team of researchers who discovered folinic acid has the potential to connect autistic children to the world around them. We recently talked with Dr. Frye about the chance encounter with a patient 6 years ago that led him to identify the first therapy for autism that targets the disorder’s underlying path of physiological abnormalities and its core symptoms.
How can folinic acid help kids with autism?
Approximately 75% of kids with autism have 1 of the 2 antibodies that block to varying degrees the ability of folate to enter the nervous system. My recent research used standardized tests to measure a child’s language level before and after administering folinic acid in order to determine how much their communication skills improved on a standardized scale. In general, treatment resulted in a 7-point increase. That means folinic acid is at least as good as current best behavioral therapies.
Could folinic acid replace the need for therapy?
Therapy has its drawbacks — it’s intense, requires 40 hours each week to complete, and is expensive — but I don’t want to be misleading about our research. Folinic acid isn’t the only intervention autistic kids need. It could be a single component of treatment that’s integrated with speech and behavioral therapies to help kids reach communication goals that much faster. Folinic acid fixes broken physiological pathways, so children benefit even more from conventional therapies.
What sparked your interest in this use of folinic acid?
My interest actually began in 2005, when researchers discovered that children with developmental delays had cerebral folate deficiency, which meant they had low levels of folate in their central nervous system because of a blockage caused by the folate receptor autoantibody. The researchers also noticed that a lot of the kids had features of autism. By happenstance, I saw a patient in 2010 who was autistic and had cerebral folate deficiency. That made we wonder how many other kids with autism had problems with folate being transported to the nervous system.
How did you examine that possibility?
We assessed autistic kids with folate receptor autoantibodies who were treated with high-dose folinic acid for an average of 4 months. We then asked their parents to fill out a questionnaire indicating whether certain symptoms of autism improved or got worse. The parents consistently observed improvements in verbal and non-verbal communication. Our current double-blind, placebo-controlled study took that research to the next level to confirm that high-dose folinic acid seems to improve verbal communication in autistic children. The previous study included only kids who were positive for the folate autoantibody. In this study, we included kids who were positive and negative, so we were able to see if the folate antibody predicted response to treatment. We found that it did.
How do current medication therapies
for autism compare in terms of efficacy and safety profile?
This is a very important point. Antipsychotics are the only approved medication therapy for autism. They’re indicated for irritability, which is not a core symptom, and can cause changes to cardio-metabolic parameters such as blood glucose stability, and triglyceride and cholesterol levels. Antipsychotics can also cause significant weight gain and increase risk of type 2 diabetes. Those are some serious side effects. We believe folinic acid is targeting a core symptom of autism and is relatively safe. Calcium folinate, which we used in this study, has demonstrated a strong safety profile at much higher doses to rescue oncology patients from the side effects of chemotherapy. The therapy’s safety profile is based on a great deal of real-world experience, so we’re confident that it’s a safe treatment for autistic children.
—Interview conducted by Dan Cook