Sodium Channelopathies and Novel Viral/non-viral Vectors for their Gene Therapy

Channelopathies are a group of neurological disorders that is caused by various genetic or acquired factors. In this disease, ions channels, a transmembrane protein channel responsible for the regulation of electrochemical gradient in the neuronal cells are disrupted. The disruption leads to myriads of neurological havoc due to abrupt synaptic transmission, voltage potential, and hyperexcitability of ions channels. Defective ions channels expedite the development of various disorders i.e., migraine, epilepsy, small fiber neuropathy, erthemalgia, paroxysmal pain disorder, dravet syndrome, and congenital insensitivity to pain, and others. These defects are commonly caused by deleterious mutational events in the ion channel gene encoding regions (SCN9A, SCN10A, and SCN11A). These regions encode for alpha subunits of sodium voltage gated channels (NaV 1.7, 1.8, and 1.9) that have notable importance in normal neuronal functioning. In these regions, usually, missense mutations are observed that cause improper protein folding making sodium channels excited for longer periods. The excitation is mainly manifested in peripheral and sympathetic neurons that contribute towards the development of chronic or acute pain or no pain sensation at all. There are several studies in the pipeline trying to elucidate the molecular mechanism of pain in relation to channelopathies. The lack of efficient pain models and shortcomings in the ill elucidate nature of the disease is somehow impeding the progress and development of novel therapies. But the existing literature revealed various pathways and targets that could be fruitful for different gene therapy interventions as opioids, analgesics, and non-steroidal anti-inflammatory drugs used to treat these conditions are imposing significant side effects and cellular proteins are developing resistance for these molecules, hence making them obsolete.

Keywords: Channelopathies, Gene Delivery, Ion Channels, Viral and Non-viral Vectors, Voltage Gated Channels.