Prescription doses of folinic acid could reduce several autism symptoms, study shows, pointing towards predicting likely responders

A new study led by Dr Frye of the Arkansas Children’s Research Institute has shown that prescription doses of folinic acid may help children with autism better develop verbal communication skills.

Forty-eight children with autism spectrum disorder and language impairment were randomized to receive twelve weeks of either high-dose folinic acid (leucovorin) treatment or a placebo. Children in the experimental group were found to demonstrate notably improved verbal communication skills.

The researchers also identified specific blood markers, namely autoantibodies to folate receptors, that predict which individuals have the best chance to respond to this treatment.

“Improvement in verbal communication was significantly greater in participants receiving folinic acid as compared with those receiving the placebo… Irritability, lethargy, stereotyped behavior, hyperactivity, inappropriate speech and total score on the ABC significantly improved in the folinic acid group as compared with the placebo group.”

The findings were published in Molecular Psychiatry. Detailed discussion on the findings and its implications, in the form of Q&A with the Dr Frye, the main author, can be seen here. Follow up studies with larger sample sizes need to be conducted to verify these results. From the study’s press release:

“Scientific research has previously linked autism to abnormalities in the metabolism of folate as well as genes that are involved in folate metabolism. Certain studies have also shown that the offspring of women who took folate supplements before conception and during pregnancy had a lower risk of having a child with ASD.”

About ten years ago a condition, known as cerebral folate deficiency (CFD), was described in which the concentration of folate is below normal in the central nervous system but not in the blood. Many children with CFD had ASD symptoms and responded well to treatment with high-dose folinic acid.

Previously Frye’s team could show that folate receptor autoantibodies were found with a high prevalence in children with ASD. In the current study, these researchers found that participants with folate receptor autoantibodies had a more favourable response to the folinic acid treatment.

“This leads the way to a test that might be useful for clinicians to determine if high-dose folinic acid might be a treatment for a particular child with ASD. The deleterious effects of folate receptor antibodies on brain development and function are now confirmed in a laboratory rat model.”

Other therapeutic options for autoimmune cerebral folate deficiency syndrome are corticosteroids and milk-free diet.

This article is part of Treating Autism Clinical & Research Newsletter: Issue 1

References:

Frye, R.E. et al. (2016). Folinic acid improves verbal communication in children with autism and language impairment: A randomized double-blind placebo-controlled trial, Molecular Psychiatry, doi: 10.1038/mp.2016.168.

Further reading:

Desai A, Sequeira JM, Quadros EV. (2016) Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism. Mol Psychiatry. Sep 20. doi: 10.1038/mp.2016.153.

Frye RE, Delhey L, Slattery J, et al. (2016) Blocking and Binding Folate Receptor Alpha Autoantibodies Identify Novel Autism Spectrum Disorder Subgroups. Front Neurosci. Mar 9;10:80. doi: 10.3389/fnins.2016.00080.

Ramaekers VT, Sequeira JM, Blau N, et al. (2008) A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. May;50(5):346-52. doi: 10.1111/j.1469-8749.2008.02053.x. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715943.