Novel Gene Therapy Shows Promise in Targeting a Mutation Linked to Epilepsy
November 13, 2024
Article Published by Medical Xpress
Researchers are testing a novel gene therapy approach for a rare genetic form of epilepsy linked to a mutation in the KCNA2 gene in the human brain, which is associated with recurring seizures. A specialized treatment called a Gapmer antisense oligonucleotide (ASO) is designed to specifically target and break down faulty ribonucleic acids (RNA) while keeping normal gene function intact. Using this RNA therapy approach led to a notable decrease in a problematic potassium channel protein encoded in the KCNA2 gene, which helped restore normal potassium flow and reduce excessive neuron activity linked to epilepsy. “Epilepsy is associated with hyper-excitable neurons, and potassium helps dampen the excitability levels. The potassium channel encoded by KCNA2 is like a door that controls the potassium ion flow on the surface of the cells. When the gene is mutated, the door fails to work and potassium cannot be released to control neuron activity, which results in epilepsy,” said Assistant Professor Huang Hua at Yong Loo Lin School of Medicine, National University of Singapore. “Our therapy targets the faulty RNA in the gene and ‘fixes the door,’ so that potassium can flow and regulate the neuron activity levels.” The new Gapmer technology being worked on by the research team could also be adapted to target other mutations in the same gene or other ion channel genes—opening the possibility of creating personalized treatments for different KCNA2-related issues, potentially offering hopeful outcomes for patients with rare forms of epilepsy that are unresponsive to standard medications.