Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype. Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients. Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple Read more

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners. The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and Read more

Neutrophils flood lungs in severe COVID-19

In the lungs of severe COVID-19 patients, neutrophils camp out and release inflammatory cytokines and tissue-damaging Read more

Dravet syndrome

Oxytocin delivery via nanoparticles

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.

The nanoparticle approach could be used for other neuropeptides such as neuropeptide Y, proposed as a treatment mode for anxiety disorders/PTSD, and hypocretin, the missing molecule in narcolepsy. Murnane formed a company when he was at Mercer to develop the technology.

Posted on by Quinn Eastman in Neuro Leave a comment

Nerve gas, angel dust and genetic epilepsy

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.

What condition? Dravet syndrome/GEFS+ Epilepsy-aphasia syndrome
What gene is mutated? SCN1A – sodium ion channel GRIN2A – NMDA receptor subunit
What is the beneficial drug? Huperzine A Memantine
How does the drug work? Acetylcholinesterase inhibitor NMDA receptor antagonist
Other drugs that use the same mechanism Alzheimer’s medications such as donepezil

Irreversible + stronger: insecticides, nerve gas

Ketamine, phencyclidine (aka PCP)
Posted on by Quinn Eastman in Neuro Leave a comment