Early Treatment of Language Impairment in Young Children with Autism Spectrum Disorder with Leucovorin Calcium
Abstract
Autism spectrum disorder (ASD) is a devastating neurodevelopmental disorder with life-long consequences that affect young children during critical times in their development. The latest estimates from the Centers for Disease Control suggest that 1 in 68 individuals in the United States (~1-2%) are affected by an ASD. ASD is behaviorally defined by impairments in three core areas of development, including deficits in communication and social interactions and the presence of restrictive and repetitive behaviors. The prevalence of ASD has demonstrated a dramatic rise over the past two decades and continues to rise. Although there is debate as to the reason behind this increase, the fact remains that 1-2% of children are affected with an ASD without an effective treatment. Currently, there is no Food and Drug Administration (FDA)-approved medical therapy that is either indicated for core ASD symptoms or that addresses biological abnormalities in cellular function. The only approved FDA drugs, both anti-psychotic drugs, are indicated for an associated, not core, ASD symptom, namely irritability. These drugs cause serious cardiometabolic adverse effects in a short time, increase the risk of developing type II diabetes, and potentially can cause a permanent movement disorder. The standard-of-care treatment for core ASD symptoms is behavioral therapy, which requires full-time engagement of a one-on-one therapist over several years. Although such therapy may help modify behavior, it does not address the underlying biological abnormalities associated with ASD and thus probably has little effect on the underlying biological causes of the disease. Thus, safe, well-tolerated effective medical treatments that address underlying physiological abnormalities associated with ASD, like the ones described in this proposal, could greatly accelerate attaining optimal outcomes. Few treatments addressing the underlying physiological abnormalities and core ASD symptoms have been studied in clinical trials. Studies from the investigators of this trial have documented that abnormalities in folate metabolism that occur in a significant subgroup of children with ASD can be treated with leucovorin calcium, a reduced form of folate that bypasses blockages in transport into the brain and bypasses several of the initial enzymes in the folate cycle that are known to have polymorphism, which decrease their function. We have demonstrated in both an open-label and double-blind, placebo-controlled (DBPC) trial that leucovorin calcium improves verbal communication and language in a wide range of children with ASD, as well problematic behaviors, and is well tolerated without significant adverse effects. In addition, in our most recent DBPC trial, we demonstrated that an important blood test is predictive of response to leucovorin calcium treatment. Thus, we believe that these safe and effective treatments, when combined, can have a substantial impact on core and associated ASD symptoms while addressing underlying folate metabolism abnormalities. The current trial is proposed to determine whether this treatment is effective in young, recently diagnosed children with ASD and whether the treatment also improves social communication as well as language. Thus, this study proposes to study a liquid formulation of leucovorin calcium that can easily be given to young children in a 12-week DBPC clinical trial with 12-week open-label extension (in which all children receive leucovorin treatment) in order to provide strong evidence that it improves core and associated ASD symptoms and biological disturbances associated with ASD and to confirm its safety profile. We will use a special tool to measure the important core symptom of social communication so that we can demonstrate that leucovorin calcium treats the core social deficit associated with ASD, as well as the language abnormalities. We also aim to determine which biomarkers are able to select i
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910178
Entities
People
- Richard E Frye
Organizations
- United States Army