Amidst the tumult in the nation’s capital, a quieter reckoning was taking place this week for the Moderna COVID-19 vaccine clinical trial. Lab Land has been hearing from Emory-affiliated study participants that they’re finding out whether they received active vaccine or placebo.
For example, Emory and Grady physician Kimberly Manning, who had written about her participation in the Moderna study in a Lancet essay, posted on Twitter Tuesday. She discovered she had received placebo, and Read more
The neuropeptide oxytocin, known for promoting social interactions, has attracted interest as a possible treatment for autism spectrum disorder. A challenge is getting the molecule past the blood-brain barrier. Many clinical studies have used delivery via nasal spray, but even then, oxytocin doesn’t last long in the body and shows inconsistent effects.
Emory neuroscientist Andrew Escayg has been collaborating with Mercer/LSU pharmacologist Kevin Murnane on a nanoparticle delivery approach that could get around these obstacles. One of Escayg’s primary interests is epilepsy — specifically Dravet syndrome, a severe genetic form of epilepsy — and oxytocin has previously displayed anti-seizure properties in animal models.
Escayg and Murnane’s recent paper in Neurobiology of Disease shows that when oxytocin is packaged into nanoparticles, it can increase resistance to induced seizures and promote social behavior in a mouse model of Dravet syndrome.
This suggests properly delivered oxytocin could have benefits on both seizures and behavior. In addition to seizures, children and adults with Dravet syndrome often have autism – see this Spectrum News article on the connections.
Escayg reports he is planning a collaboration with oxytocin expert Larry Young at Yerkes, who Tweeted “This is a promising new area of oxytocin research” when the paper was published. Senior postdoc Jennifer Wong has already been working on extending the findings to other mouse models of epilepsy and adding data on spontaneous seizure frequency.
Imagine the game of pick up sticks. It’s hard to extract one stick from the pile without moving others. The same problem exists, in a much more complex way, in the brain. Pulling on one gene or neurotransmitter often nudges a lot of others.
Andrew Escayg, PhD
That’s why a recent paper from Andrew Escayg’s lab is so interesting. He studies genes involved in epilepsy. Several years ago, he showed that mice with mutations in the SCN8A gene have absence epilepsy, while also showing resistance to induced seizures. SCN8A is one of those sticks that touches many others. The gene encodes a voltage-gated sodium channel, involved in setting the thresholds for and triggering neurons’ action potentials. Mutating the gene in mice modifies sleep and even enhances spatial memory.
Escayg’s new paper, with first author Jennifer Wong, looks at the effect of “knocking down” SCN8A in the hippocampus in a mouse model of mesial temporal lobe epilepsy. This model doesn’t involve sodium channel genes; it’s generated by injection of a toxin (kainic acid) into the brain. The finding suggests that inhibiting SCN8A may be applicable to other forms of epilepsy. Escayg notes that mesial temporal lobe epilepsy is one of the most common forms of treatment-resistant epilepsy in adults.
Knocking down SCN8A in the hippocampus 24 hours after injection could prevent the development of seizures in 90 percent of the treated mice. “It is likely that selective reduction in Scn8a expression would have directly decreased neuronal excitability,” the authors write. It did not lead to increased anxiety levels or impaired learning/memory.
Last week, Lab Land noticed similarities between two independent lines of research from the Escayg and Traynelis/Yuan labs at Emory. Both were published recently and deal with rare forms of genetic epilepsy, in which molecular understanding of the cause leads to individualized treatment, albeit with limited benefit.
Both conditions are linked to an excess of neuronal excitation, and both can be addressed using medications that have also been tested for Alzheimer’s. A critical difference is that memantine is FDA-approved for Alzheimer’s, but huperzine A is not.
Please check out our feature in Emory Medicine magazine about two sisters with NGLY1 deficiency. This rare genetic disorder was identified only a few years ago, and now a surge of research is directed toward uncovering its mysteries.
The Stinchcombs are amazing. Seth Mnookin’s July 2014 piece in the New Yorker, and especially, his comments at the end of an interview with The Open Notebook drove me to contact them. “The father cares for the two girls with this disease full time. The mother is working insane hours. And while all this is going on, they’re the most good-natured … I don’t know, they just seem like they’re happy.”