Results of valacyclovir, valganciclovir, artesunate for the treatment of reactivated EBV-, HHV-6-, HHV-7-infections in children with autism spectrum disorders associated with genetic deficiency of the folate cycle

Autism spectrum disorders (ASD), which currently affect at least 1 % of the modern child population and continue to increase in prevalence, are a global problem that requires urgent attention. However, the FDA has not yet approved any drug to modify the course of ASD in children or to treat mental illness. The results of 5 recent meta-analyses and systematic reviews of randomized controlled trials demonstrate the association of ASD with genetic deficiencies of folic acid cycle enzymes (GDFC), which sheds light on the pathogenetic pathways of the formation of a state of transmethylation disorders, persistent oxidative stress, immunodeficiency and related immune dysregulation, and reactivation of opportunistic infections, which are considered important pathways of brain damage in children with ASD.

According to the data of a systematic review by Hughes H.K. et al. on the state of the immune system, children with ASD have impaired cytokine balance, quantitative disorders of immunocompetent cells, signs of persistent neuroglial inflammation in the CNS, defects in the functioning of the adaptive and innate immune systems, pathological deviations in serum concentrations of immunoglobulins of different classes and subclasses, as well as signs of autoimmune reactions to neurons, myelin, and extracerebral autoantigens.

Due to immune dysfunction in ASD, resistance to a number of microorganisms is reduced. A number of clinical reports and results of controlled studies have been published on the development of severe infections caused by opportunistic and conditionally pathogenic microbial agents in children with ASD. This phenomenon can be explained by the damage to the immune system induced by both GDFC and other genetic abnormalities associated with ASD. One of the key intracellular opportunistic agents that undergo reactivation in the body of children with ASD is herpesviruses. Currently, the typical development of infections caused by various types of herpes in children with ASD has been repeatedly reported, including reactivation of HSV-1, EBV, CMV and HHV-6.