Phoenix Children’s Receives $1 Mil to Study if Leucovorin Help Autistic Children

Jan 14, 2019 | Autism, CNS, Price Watch, Pricing


AZBig Media reports that the Barrow Neurological Institute (BNI) at Phoenix Children’s Hospital will benefit from two research grants supporting clinical trials for children with autism spectrum disorder (ASD).  Richard E. Frye, MD, PhD, Professor of Neurology at Phoenix Children’s Hospital is the principal investigator and recipient of the grant.  Dr. Frye has been studying autism and neurodevelopmental abnormalities for decades.  Both of the grants will be used by Dr. Frye to test the effectiveness of leucovorin (folinic acid). The funder is Autism Speaks. More than 80 patients ages 2 to 5 with ASD will enroll in the Autism Speaks study over the course of three years. Certain patients will have the opportunity to participate in the study shortly following ASD diagnosis. The trial will use a liquid form of leucovorin to enhance development of brain-cell receptors that respond to naturally occurring folate. 

The new Autism Speaks grant comes on the heels of a $3 million National Institute of Health (NIH) grant Dr. Frye received prior to joining Phoenix Children’s. With the NIH grant, Dr. Frye currently leads a multi-center clinical trial to study the effects of leucovorin on language for children ages 5 to 12 with ASD. This study’s collaborators include Harvard University and Emory University. 

What is Leucovorin?  It is approved by the FDA to prevent harmful effects of methotrexate (Rheumatrex, Trexall; cancer chemotherapy medication) when methotrexate is used to treat certain types of cancer. Leucovorin is also used to treat people who have accidentally received an overdose of methotrexate or similar medications. Leucovorin is in a class of medications called folic acid analogs. It works by protecting healthy cells from the effects of methotrexate or similar medications while allowing methotrexate to enter and kill cancer cells.

What about the current study focusing on treatment of language challenges? The study is scheduled to end in 2023. The sponsor is Emory University and collaborators include Phoenix Children’s Hospital, Harvard University and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The purpose of the study is to determine the effectiveness of folinic acid (leucovorin) in the treatment of language problems with children with autism spectrum disorder.  The study team seeks to enroll 162 patients across three centers over a 5-year period-participation lasts between 12 and 24 weeks.

What other Research is Relevant? In March 2013 a group of researchers published a summary of a autism spectrum disorder and leucovorin study noting that cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood–brain barrier. Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated. In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case. Children with FRAs were treated with oral leucovorin calcium (2 mg kg−1 per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment. Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.

What does Leucovorin current cost? According to cost aggregator GoodRX the lowest price for the common version is around $7.14 or 48% off the average retail price of $13.75

Lead Research/Investigator

Richard E. Frye, MD, PhD

1 Comment

  1. Salosh Saayman

    Can my grandson, be one of the chosen ones for this experiment.My email add is

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