RARE DISEASE
Fetal alcohol syndrome
Fetal alcohol syndrome
Fetal alcohol syndrome
Synonyms: ARBD, ARND, Alcohol-related birth defects, Alcohol-related neurodevelopmental disorder, FAS, FASD, Fetal alcohol spectrum disorders
Synonyms: ARBD, ARND, Alcohol-related birth defects, Alcohol-related neurodevelopmental disorder, FAS, FASD, Fetal alcohol spectrum disorders
Synonyms: ARBD, ARND, Alcohol-related birth defects, Alcohol-related neurodevelopmental disorder, FAS, FASD, Fetal alcohol spectrum disorders
Drug discovery
0
drugs
With orphan designations
Overview
Fetal alcohol syndrome (FAS) is the most severe fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure. It is characterized by distinct facial dysmorphology (e.g., smooth philtrum, thin vermilion border), growth retardation, and neurodevelopmental impairments including cognitive deficits, behavioral challenges, and lifelong functional limitations [1][6][16]. While preventable, FAS has no cure, necessitating early multidisciplinary interventions to optimize outcomes [1][3].
Therapies
Multidisciplinary care: Developmental screenings, neurobehavioral assessments, and specialist referrals (neurology, mental health, occupational therapy) [1][3].
Pharmacotherapy: Stimulants (e.g., methylphenidate) for ADHD symptoms; mood stabilizers for comorbid conditions [3][8].
Behavioral/educational interventions: Parent training, social skills programs, and individualized education plans to address cognitive and adaptive deficits [8][18].
Categories: rare developmental anomalies during embryogenesis, rare disorders due to toxic effects, rare otorhinolaryngological diseases, rare surgical maxillo-facial diseases, rare teratologic disorders
Research Papers
1,481 drug discovery papers about Fetal alcohol syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,481 drug discovery papers about Fetal alcohol syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-24 | Hesperidin mitigates cognitive and anxiety-like deficits by enhancing hippocampal antioxidant defenses, reducing neuroinflammation, and preventing neuronal apoptosis in a third-trimester-equivalent rat model of developmental ethanol neurotoxicity.
Ethanol exposure during brain development has been associated with hippocampal oxidative stress, neuroinflammation, and apoptosis, resulting in lasting cognitive and emotional deficits characteristic of fetal alcohol spectrum disorders (FASD). This study evaluated the neuroprotective potential of Hesperidin, a citrus flavanone with antioxidant and anti-inflammatory actions, against developmental ethanol neurotoxicity. Neonatal Wistar rats received ethanol (5.25 g/kg/day; 11.9% v/v) from postnatal days 2-10 and were subsequently treated intraperitoneally with Hesperidin (25, 50, or 100 mg/kg). Behavioral testing on days 39-45 using the Elevated Plus Maze (EPM) and Morris Water Maze (MWM) showed that ethanol markedly decreased open arm time (Oat%) and entries (OAE%) (P < 0.001, P < 0.01 vs Control), increased escape latency (P < 0.001), and reduced probe target time (P < 0.001 vs Control). Hesperidin at 50 and 100 mg/kg improved all indices (P < 0.05-0.01 vs Ethanol). Ethanol elevated hippocampal MDA and TNF-α (P < 0.001) while decreasing SOD (P < 0.01) and GSH-Px (P < 0.001), Hesperidin normalized these values (P < 0.01-0.001 vs Ethanol). GFAP and cleaved caspase-3 immunoreactivity were also reduced by hesperidin (P < 0.001 vs Ethanol). Overall, Hesperidin afforded dose-dependent neuroprotection by mitigating oxidative stress, inflammation, and apoptosis, thereby improving ethanol-induced behavioral impairments.
2026-06-22 | Epileptiform Discharges Drive Unique High-frequency Oscillations Within the Retrosplenial Cortex of Mice with Third Trimester Alcohol Exposure.
Fetal Alcohol Spectrum Disorders (FASDs) are associated with alterations in learning and memory that persist throughout the lifespan. Thus, determining the neural mechanisms driving these alterations has the potential to identify novel therapeutic targets for improving memory in those with FASD. Given the newly realized role of the Retrosplenial cortex (RSC) for learning and memory, as well as the profound neural apoptosis that exposure to alcohol during development causes to this brain region, we recorded electrophysiological activity from mice exposed to alcohol during the third trimester-equivalent developmental time period. We observed a large number of Epileptiform Discharges (EDs) in alcohol-exposed subjects compared to controls, which were found to drive with High-frequency Oscillations (HFOs). Furthermore, many features of HFOs (amplitude/duration/etc.) were found to be directly proportional to the temporal distance from ED onset. These findings identify EDs for the first time as a critical feature in a preclinical model of FASD, and suggest their relationship to RSC HFOs may be a key mechanism driving memory alterations.
2026-06-12 | The Effects of Developmental Ethanol Exposure & Postnatal Choline Supplementation on Long-Term Choline Metabolism.
Prenatal alcohol exposure (PAE) can disrupt development, leading to alterations in physical, health, and behavioral outcomes, referred to as fetal alcohol spectrum disorders (FASD). Although alcohol likely impacts fetal development through many mechanisms, PAE could impact metabolism of choline, an essential nutrient that is important for brain development and function. Importantly, both preclinical and clinical studies show that choline supplementation can improve performance on hippocampal-dependent behavioral tasks, even when administered postnatally. However, the mechanisms by which choline mitigates prenatal alcohol-induced neurocognitive deficits are not well understood. Thus, the present study examined whether PAE leads to long-lasting changes in choline metabolism in the hippocampus and plasma of adolescent animals and if effects are modified by choline. From postnatal day (PD) 4-9, rat pups were given ethanol (EtOH; 5.25 g/kg/day) or sham intubations. From PD 10-30, subjects received s.c. choline chloride (100 mg/kg/day) or saline. Plasma and hippocampus were collected on PD 35 and choline metabolite levels were analyzed. Neither EtOH nor choline led to long-lasting changes in choline levels. However, EtOH-exposed females had reduced hippocampal betaine and plasma betaine:choline ratios. Plasma cystathionine was elevated in EtOH-exposed females treated with choline, suggesting choline activates anti-oxidative stress and anti-inflammation pathways among EtOH-exposed subjects. Choline alone increased homocysteine among females. In contrast, choline supplementation increased plasma SAM:SAH ratios in EtOH-exposed males, suggesting choline is modifying DNA methylation. Overall, these results provide insights to sex-specific mechanisms of action in which choline supplementation alters choline metabolic pathways in FASD.
2026-06-24 | Hesperidin mitigates cognitive and anxiety-like deficits by enhancing hippocampal antioxidant defenses, reducing neuroinflammation, and preventing neuronal apoptosis in a third-trimester-equivalent rat model of developmental ethanol neurotoxicity.
Ethanol exposure during brain development has been associated with hippocampal oxidative stress, neuroinflammation, and apoptosis, resulting in lasting cognitive and emotional deficits characteristic of fetal alcohol spectrum disorders (FASD). This study evaluated the neuroprotective potential of Hesperidin, a citrus flavanone with antioxidant and anti-inflammatory actions, against developmental ethanol neurotoxicity. Neonatal Wistar rats received ethanol (5.25 g/kg/day; 11.9% v/v) from postnatal days 2-10 and were subsequently treated intraperitoneally with Hesperidin (25, 50, or 100 mg/kg). Behavioral testing on days 39-45 using the Elevated Plus Maze (EPM) and Morris Water Maze (MWM) showed that ethanol markedly decreased open arm time (Oat%) and entries (OAE%) (P < 0.001, P < 0.01 vs Control), increased escape latency (P < 0.001), and reduced probe target time (P < 0.001 vs Control). Hesperidin at 50 and 100 mg/kg improved all indices (P < 0.05-0.01 vs Ethanol). Ethanol elevated hippocampal MDA and TNF-α (P < 0.001) while decreasing SOD (P < 0.01) and GSH-Px (P < 0.001), Hesperidin normalized these values (P < 0.01-0.001 vs Ethanol). GFAP and cleaved caspase-3 immunoreactivity were also reduced by hesperidin (P < 0.001 vs Ethanol). Overall, Hesperidin afforded dose-dependent neuroprotection by mitigating oxidative stress, inflammation, and apoptosis, thereby improving ethanol-induced behavioral impairments.
2026-06-22 | Epileptiform Discharges Drive Unique High-frequency Oscillations Within the Retrosplenial Cortex of Mice with Third Trimester Alcohol Exposure.
Fetal Alcohol Spectrum Disorders (FASDs) are associated with alterations in learning and memory that persist throughout the lifespan. Thus, determining the neural mechanisms driving these alterations has the potential to identify novel therapeutic targets for improving memory in those with FASD. Given the newly realized role of the Retrosplenial cortex (RSC) for learning and memory, as well as the profound neural apoptosis that exposure to alcohol during development causes to this brain region, we recorded electrophysiological activity from mice exposed to alcohol during the third trimester-equivalent developmental time period. We observed a large number of Epileptiform Discharges (EDs) in alcohol-exposed subjects compared to controls, which were found to drive with High-frequency Oscillations (HFOs). Furthermore, many features of HFOs (amplitude/duration/etc.) were found to be directly proportional to the temporal distance from ED onset. These findings identify EDs for the first time as a critical feature in a preclinical model of FASD, and suggest their relationship to RSC HFOs may be a key mechanism driving memory alterations.
2026-06-12 | The Effects of Developmental Ethanol Exposure & Postnatal Choline Supplementation on Long-Term Choline Metabolism.
Prenatal alcohol exposure (PAE) can disrupt development, leading to alterations in physical, health, and behavioral outcomes, referred to as fetal alcohol spectrum disorders (FASD). Although alcohol likely impacts fetal development through many mechanisms, PAE could impact metabolism of choline, an essential nutrient that is important for brain development and function. Importantly, both preclinical and clinical studies show that choline supplementation can improve performance on hippocampal-dependent behavioral tasks, even when administered postnatally. However, the mechanisms by which choline mitigates prenatal alcohol-induced neurocognitive deficits are not well understood. Thus, the present study examined whether PAE leads to long-lasting changes in choline metabolism in the hippocampus and plasma of adolescent animals and if effects are modified by choline. From postnatal day (PD) 4-9, rat pups were given ethanol (EtOH; 5.25 g/kg/day) or sham intubations. From PD 10-30, subjects received s.c. choline chloride (100 mg/kg/day) or saline. Plasma and hippocampus were collected on PD 35 and choline metabolite levels were analyzed. Neither EtOH nor choline led to long-lasting changes in choline levels. However, EtOH-exposed females had reduced hippocampal betaine and plasma betaine:choline ratios. Plasma cystathionine was elevated in EtOH-exposed females treated with choline, suggesting choline activates anti-oxidative stress and anti-inflammation pathways among EtOH-exposed subjects. Choline alone increased homocysteine among females. In contrast, choline supplementation increased plasma SAM:SAH ratios in EtOH-exposed males, suggesting choline is modifying DNA methylation. Overall, these results provide insights to sex-specific mechanisms of action in which choline supplementation alters choline metabolic pathways in FASD.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.