Targeting Maladaptive Myelination in Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy in which seizures, such as atypical absence seizures, progressively increase despite treatment. Dr. Juliet Knowles and her team previously demonstrated that a change (known as plasticity) in the white matter or myelin of the brain contributed to the progression of typical absence seizures. Myelin is a substance that acts as a form of insulation around the nerve cells of the brain and is essential for the conduction of electrical impulses between neurons and for the proper functioning of the brain. They also showed that preventing this change with a type of drug called a histone deacetylase inhibitor (HDACI) significantly reduced the progression of these seizures. For this project, the team will study whether HDACIs can prevent myelin plasticity and seizure progression in a mouse model of LGS. These studies will help determine the therapeutic potential for targeting myelin plasticity in LGS. 

This grant is co-funded with the Isaiah Stone Foundation.