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.
