Lissencephaly is a devastating developmental disorder due to defective neuronal migration. The mutated gene LIS1 is a regulatory molecule of cytoplasmic dynein. LIS1 has a short half-life by calpain dependent protein degradation. We have devised a novel strategy for lissencephaly using calpain inhibitors. Currently, we are investigating therapeutic efficiency of calpain inhibitors using LIS1 mutant mice as a model for lissencephaly.
An effective therapeutic intervention for lissencephaly has not been established. Our previous study indicates that calpain inhibitors will become a beneficial approach for lissencephaly through augmentation of LIS1 protein. In addition, our strategy may be applicable to other genetic diseases due to haploinsufficiency.
