Interneuron-specific therapeutics to normalize neuronal cell excitability and treat Dravet syndrome

摘要

Expression of an effector gene (e.g., SCN1A-encoding polynucleotide, Gq-DREADD-encoding polynucleotide, or PSAM-encoding polynucleotide) contained in the vector to PV-expressing GABAergic interneurons in the brain or to a neuronal cell population A therapeutic viral vector, in particular a recombinant adeno-associated virus (rAAV) vector, designed to contain an enhancer sequence that specifically restricts is provided. rAAV vectors, compositions and methods thereof are used to treat subjects suffering from neuropathological, seizure, pharmacologically-refractory forms of epilepsy, including Dravet syndrome (DS), a form of infantile epilepsy associated with severe seizures, cognitive impairment and premature death. It is useful in treating DS, which is the cause of SCN1A.This is because it involves loss of function of the sodium channel encoded by the gene. The described vectors advantageously address the origin of the disease by restoring the excitatory-inhibitory balance by means of gene-therapy (with SCN1A) or pharmacogenetics, thereby addressing the underlying cause of the effector gene for an appropriate interneuron or neuronal cell population with specificity and sensitivity. restore expression.