Shedding light on the genetic alterations involved in epilepsy and the most effective treatments in children, but also on the role played by the intestinal microbiota. This is the objective of macro-project coordinated by the Federico II University of Naples within Mnesys, the ‘Italian Cern’ for the study of the brain. Epilepsy, which in industrialized countries affects on average 1 person in 100, mainly affects children: in 60% of cases, in fact, it appears before puberty, between the ages of 13-14, with possible negative consequences on psychomotor development and repercussions on social plan.
Most epilepsies do not have a specific cause or clear hereditary transmission, but in approximately 40% of cases it is possible to identify a genetic origin, i.e. the presence of variants in genes directly related to brain function. This is the case of variations in the Kcna3 potassium channel gene, cell membrane proteins, which can cause epileptic and developmental encephalopathies in childhoodaccording to an international study coordinated by the groups of Maurizio Taglialatela, professor of Pharmacology at Federico II, and Johannes Lemke, of the University of Leipzig, and published in the ‘Annals of Neurology’.
In the study, explains Taglialatela, “individuals carrying a Kcna3 variant were selected and 86% of these showed epileptic and developmental encephalopathies with marked language delay with or without motor delay, intellectual disability, epilepsy and spectrum disorder autistic. The study also showed that iThe antidepressant drug fluoxetine could represent a potential targeted treatment for individuals carrying certain Kcna3 variants“.
L’The objective is also to identify the most effective treatments for children with epilepsy. Although it is a disease that mainly affects children, treatment in pediatric age is hampered by the low specificity of the available therapies. “Historically, studies on the effectiveness of drugs against convulsions have been conducted on adults and, only at a later time and not in a systematic way, on children. The judgment of effectiveness is therefore produced, in a very indirect way, through a deductive process deriving from studies on adults, inevitably conducted on populations with forms of epilepsy barely comparable to those typical of childhood – underlines Taglialatela – One of the objectives of Mnesys’ Spoke 3 is precisely to study the mechanisms responsible for the epilepsy and to understand how these may offer new treatment opportunities for pediatric epilepsy”.
The spotlight is also on the connection between intestinal microbiota and the brain as a potential causal mechanism in acquired epilepsy, which was investigated by research published in ‘Neurobiology of Disease’ in March, conducted in collaboration between the groups coordinated by Pasquale Striano, of the University of Genoa and of the Irccs Gaslini of Genoa, and of Teresa Ravizza, of the Irccs Mario Negri Pharmacological Research Institute of Milan.
“Status epilepticus was induced in animal models and the presence of spontaneous seizures was monitored 5 months after the initial episode. 56% developed epilepsy and, in comparison with the guinea pigs that did not show seizures and with those of the control group, structural, cellular and molecular alterations were found that reflect a dysfunctional intestine, specifically associated with epilepsy – says Ravizza – The study therefore provides new evidence of long-term intestinal alterations, together with metabolic changes linked to microbiota, which occur specifically in rats that develop epilepsy after brain injury early in life.”
