This technology describes a method for selectively eliminating dynamin-1 (DNM1) variants for the treatment of DNM1-associated neurological diseases such as severe developmental and epileptic encephalopathy (DEE).
Mutations in dynamin-1 (DNM1) result in severe developmental and epileptic encephalopathy (DEE), with most pediatric patients unresponsive to current antiepileptic drugs. For a majority of patients traditional antiepileptic drugs are not effective, leaving >80% of patients with intractable seizures. Approximately 20 pathogenic DNM1 variants have been identified and attributed to playing a causal role in the neurological symptoms of the disease. Therefore, a gene therapy approach targeting pathogenic DNM1 may provide an effective treatment approach.
This method selectively eliminates DNM1 variants for the treatment of DNM1-associated neurological diseases. Artificial microRNAs are used to eliminate DNM1 alleles in a nonspecific manner, thereby knocking down DNM1 expression entirely. Simultaneously, exogenous DNM1 are expressed via adeno-associated virus (AAV) delivery, thereby rescuing wild-type expression of DNM1. This combinatorial treatment selectively targets pathogenic variants while restoring the function of wildtype DNM1, which may allow for more effective treatment of DEE.
IR CU21345, CU21347
Licensing Contact: Joan Martinez