Investigating the Therapeutic Potential of the Antioxidant Epigallocatechin Gallate in Fetal Alcohol Spectrum Disorders: Cognition and RNASeq

Prenatal alcohol exposure (PAE) impacts fetal development, leading to Fetal Alcohol Spectrum Disorders (FASD) characterized by cognitive, behavioral, and physical impairments. This study explores Epigallocatechin Gallate (EGCG), a potent antioxidant and modulator of neuronal plasticity, as a therapeutic intervention for FASD improvement. In a 12-month pilot study, patients with 40 FASD received 9 mg/kg/day of EGCG, with outcomes assessed through RNA sequencing of blood samples and neurocognitive evaluations (WISC-IV, CBCL 6-18, and NEPSY-II). Reduced levels of oxidative stress were observed after 6 months of daily treatment with EGCG, to maintain the bioavailability of the molecule in the body, with decreased levels of MDA and 8-isoprostane and increased activity of LDH. Significant neurocognitive improvements were shown after one year of treatment in Perceptual Reasoning Index (PRI) and Working Memory Index (WMI) using the WISC-IV test. CBCL test revealed an improvement in aggressive behavior scores after EGCG treatment. NEPSY-II assessment showed improvements in face memory, and delayed face memory. Interestingly, no significant improvements were observed in intelligence quotient, attention, anxiety, or depression, which affect a proportion of individuals diagnosed with FASD. Additionally, EGCG modulates molecular pathways associated with neuroinflammation, oxidative stress, immune response, and neurogenesis. This study highlights EGCG as a potential therapeutic candidate to ameliorate cognitive and behavioral deficits caused by PAE in children affected by FASD, revealing potential pathways and biomarkers that contribute to these improvements. These advancements ultimately aim to enhance the quality of life for FASD patients and their families. Overall design: RNA-seq analysis was conducted in 8 FASD patients at baseline (t0) and following 12 months of EGCG treatment (t12)