D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery

AbstractMOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in theSLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants inSLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment and epileptiform activity at the EEG after epilepsy surgery (NCT04833322). Patients were orally supplemented with D-galactose for 6  months in doses up to 1.5 g/kg/day and monitored for seizure frequency including 24-h video-EEG recording, cognition and behavioral scores, i.e., WISC, BRIEF-2, SNAP-IV, and SCQ, and quality of life measures, before and 6 months after treatment. Global response was defined by >  50% improvement of seizure frequency and/or cognition and behavior (clinical global impression of “much improved” or better). Twelve patients (aged 5–28 years) were included from three different centers. Neurosurgical tissue samples were available in all patients and revealed a brain somat ic variant inSLC35A2 in six patients (non-present in the blood). After 6  months of supplementation, D-galactose was well tolerated with just two p...
Source: Neurotherapeutics - Category: Neurology Source Type: research