The novel sodium channel modulator GS-458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy.

ABSTRACT:

Objective

De novo mutations of SCN8A, encoding the voltage-gated sodium channel Na_V 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity. Functional characterization of several SCN8A encephalopathy variants has shown that elevated persistent sodium current is one of several common biophysical defects. Therefore, specifically targeting elevated persistent current may be a useful therapeutic strategy in some cases.

Methods</

SUBMITTER: Baker EM 

PROVIDER: S-EPMC6142814 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature