Description:

Erin Baker
PhD Candidate in the Laboratory of Jennifer Kearney, PhD   

"Assessing Existing and Novel Treatments for SCN8A Encephalopathy"             

SCN8A encephalopathy is a severe form of epilepsy caused by pathogenic variants in SCN8A, encoding Nav1.6. Anticonvulsants that block voltage-gated sodium channels are often effective treatments for seizures in SCN8A encephalopathy but require high doses that risk severe side effects/toxicity. In the Scn8a-N1768D mouse model, potency of some FDA-approved sodium channel blocker (SCB) anticonvulsants is lower compared to wild-type mice. The novel SCB PRX-330 was shown to be a potent and efficacious treatment, and was previously shown to have a wider therapeutic index than existing SCB anticonvulsants. Ongoing efforts are directed towards further assessing pharmacology in cells expressing Nav1.6 using the SyncroPatch system, as well as in hippocampal slices from Scn8a-N1768D and wild-type mice. Using a combination of in vivo, ex vivo, and in vitro system described, we aim to advance targeted therapies for SCN8A encephalopathy.

Lamiaa El-Shennawy, PhD
Postdoctoral Fellow in the Laboratory of Huiping Liu, MD, PhD

"Circulating ACE2-expressing Exosomes Block SARS-CoV-2 Infection as an Innate Antiviral Mechanism"

Both convalescent plasma and engineered human monoclonal antibodies have shown therapeutic potential to treat COVID-19. Whether additional antiviral soluble factors exist in peripheral blood remains understudied. We detected dramatic increase in plasma circulating ACE2+ exosome levels in patients with severe COVID-19 pathogenesis. We demonstrated that exosomal ACE2 prevented SARS-CoV-2 pseudotype virus infection of human host cells at a 50-150-fold higher efficacy than rhACE2. Similarly, antiviral activity of exosomal ACE2 has proven to block wild-type live virus infection. Our data demonstrate that ACE2+ exosomes can serve as a decoy therapeutic and a possible innate antiviral mechanism to block SARS-CoV-2 infection.