In response to a disease-causing genetic mutation, the expression of any of the other normal genes might be up-regulated or down-regulated. This can be surveyed and measured. But is each response good or bad? Is the response trying to compensate, and restore normal function – or is it an unavoidable repercussion of the disease, and making things worse? This short review addresses this topic with regard to Dravet Syndrome.
The most interesting finding presented is that the gene encoding the SK2 calcium-activated small potassium channel is selectively down-regulated in Dravet mice. The mechanistic consequences of this are consistent with an increase in non-convulsive seizures. Therefore, a new way to treat Dravet could be to enhance the activity of calcium-activated small potassium channels. The author points out that this concept could be explored further, because there are already approved drugs that act as SK channel agonists, and they could be tested.
Isom, L. Is Targeting of Compensatory Ion Channel Gene Expression a Viable Therapeutic Strategy for Dravet Syndrome? Epilepsy Currents 2019, Vol. 19(3) 193-195 DOI: 10.1177/1535759719844780