Scorpion Venom and Epilepsy
The fourth most common neurological disease is epilepsy, a seizure disorder. It affects 1 in 26 people and can happen in any age group. Seizures are often unpredictable, making it difficult to manage. While some causes of epilepsy are related to brain injury, most are of unknown origin. A rare form of epilepsy is Dravet Syndrome (DS). DS is lifelong and appears in the first year of life and typically causes developmental delays, negatively impacts quality of life, and increases risk of Sudden Unexpected Death in Epilepsy (SUDEP). Unfortunately, it does not respond well to current anti-seizure medications. Two new treatments, Epidiolex and Stiripentol, have been FDA approved in 2018 and offer some hope.1 Mutations in the SCN1A gene appear in 80% of those with DS and abnormal function of the Nav1.1 protein negatively affect neuronal activity.2
While currently available sodium channel blocking medications can make the condition worse, recent research indicates that specific blocking of Nav1.1 channel inactivation in mice offers relief from seizures in DS. A new publication in ACS Pharmacology & Translational Science looks at novel scorpion venom components, Hj1a and Hj2a, which delay Nav1.1 inactivation. The authors previously identified a tarantula toxin, a knottin called Hm1a, which has a high specificity for Nav1.1 activation. Hj1a and Hj2a are members of the CSαß toxin family and are dual modulatory, with both α- and ß-toxin activity. Unfortunately, while the scorpion venoms lack the selectivity to Nav1.1, they can, however, be useful tools for Nav1.1 channel investigation and for the development of an analog that could offer treatment hope in the future.3
- Epilepsy Foundation. (n.d.) What is Epilepsy. https://www.epilepsy.com/learn/about-epilepsy-basics/what-epilepsy
- Dravet Syndrome Foundation. (n.d.) What is Dravet Syndrome? https://www.dravetfoundation.org/dsf-funded-research/
- C.Y. Chow, et al., ACS Pharmacology & Translational Science, 3, 119 (2020).