Beta-Carotene Derivatives as a Novel Therapy for the Prevention and Treatment of Autistic Symptoms

Golda Houri hgolda@gmail.com 1 Leah Lipsker 2 Yosefa Avraham 2 Amnon Albeck 1
1Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel
2Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication as well as restricted and repetitive behavior. The currently reported incidence of ASD is 1-2%, and it increases dramatically to 10-20% in families who already have a child with ASD. This makes it one of the major childhood diseases. To date, there is no effective way to treat or prevent ASD, and only symptomatic treatment with limited efficacy is available.

Oxytocin (OT) enhances affiliative behavior and improves social cognition. Several studies have suggested that social deficits characteristic of autism may be related to dysfunctional OT neurotransmission. Thus, administration of OT may relief ASD, however it has a short plasma half-life and poor BBB permeability.

CD38, a multifunctional ecto-enzyme expressed in immune cells and in the brain, was found critical for social behavior via regulation of OT secretion. All-trans retinoic acid (ATRA) is a potent inducer of CD38. Human in vitro and animal in vivo studies with ATRA have demonstrated significant decrease in autistic symptoms and improvement in social behavior. Since it is toxic and teratogenic, we suggested that β-carotene and its synthetic analogs could provide the basis for the development of a new drug for the prevention and treatment of autism.

Different derivatives were tested on newborn mice with ASD associated behavior, using a set of behavioral tests and measurements of biochemical parameters. According to the results, β-carotene and two derivatives exhibited best results in the behavioral tests. They also increased gene expression of OX receptor and CD38. These compounds have the potential to prevent and/or ameliorate autistic symptoms when administered after birth to newborns of families predisposed to autism.

Avraham et al. Behav. Brain Res. 2017. Early view









Powered by Eventact EMS