Lennox-Gastaut Syndrome (LGS) is a severe pediatric epilepsy syndrome that includes a characteristic EEG pattern, some degree of cognitive impairment, and multiple seizure types that respond poorly to available treatments. New therapies are needed to both better control seizures and improve other issues seen in LGS. Up to 35% of LGS cases have no obvious cause and are presumed to result from a genetic mutation. Heterozygous mutations in KCNB1 have been identified as a genetic cause in some patients with LGS. In genetic disease resulting from a heterozygous mutation, the individual has one good copy and one bad copy of the gene. A major unanswered question for KCNB1-associated LGS is whether the LGS results because one good copy is not enough, or from harmful effects of the bad copy of the gene. Based on our current understanding, we think that the bad copy exerts harmful effects and poisons the good copy. To formally investigate this, we will use a mouse model with a Kcnb1-associated LGS mutation and evaluate the effects of turning off the bad copy using a tool called antisense oligonucleotide (ASO). If we see improvement in neurological and behavioral symptoms in Kcnb1 LGS mice, it will provide evidence that harmful effects of the bad copy are responsible for the seizures and LGS. Addressing this critical gap in our knowledge will improve our understanding of LGS and pave the way for the development of an RNA-based disease-modifying therapy.
For information about the LGS Foundation
Research Grant Program Click Here.