Saliva-based SARS-CoV-2 antibody testing

As the Atlanta area recovers from Zeta, we’d like to highlight this Journal of Clinical Microbiology paper about saliva-based SARS-CoV-2 antibody testing. It was a collaboration between the Hope Clinic and investigators at Johns Hopkins, led by epidemiologist Christopher Heaney. Infectious disease specialists Matthew Collins, Nadine Rouphael and several colleagues from Emory are co-authors. They organized the collection of saliva and blood samples from Emory COVID-19 patients at several stages: being tested, hospitalized, and recovered. Read more

Peeling away pancreatic cancers' defenses

A combination immunotherapy approach that gets through pancreatic cancers’ extra Read more

Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease. The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes. The results were published online on Oct. Read more

rare diseases

Traynelis lead researcher on CureGRIN/Chan Zuckerberg award

Congratulations to the CureGRIN Foundation, which was recently awarded a capacity-building grant from the Chan Zuckerberg Initiative’s Rare as One Network. The Chan Zuckerberg Initiative is giving 30 patient advocacy groups such as CureGRIN $450,000 each over two years.

CureGRIN works closely with Emory pharmacologist Stephen Traynelis, who has been investigating rare genetic disorders affecting NMDA receptors, which play key roles in memory, learning and neuronal development. When NMDA receptor function is perturbed by mutations, symptoms appear in infancy or early childhood, usually including epilepsy and developmental delay.

For the grant, Traynelis is named as the lead researcher for the CureGRIN Foundation, with Tim Benke of Children’s Hospital Colorado as lead clinician. Traynelis is director of the Center for Functional Evaluation of Rare Variants, which hosted a gathering at Emory Conference Center that brought together several GRIN-oriented patient advocacy groups in September 2019.

Posted on by Quinn Eastman in Neuro Leave a comment

GRIN families join together for neuroscience

Editor’s note: This post was a collaboration with MMG graduate student Megan Hockman.

They were brought together by their children’s epilepsies, and by rapid advances in genetic sequencing. Only a few years ago, these families would have been isolated, left to deal with their children’s seizures and neurological problems on their own. Now, they’ve organized themselves and are shaping the future of research.

Agonist binding domains of NMDA receptors, where several disease-causing mutations can be found. Adapted from Swanger et al, AJHG (2016).

In mid-September, parents of children affected by variations in GRIN genes gathered at Emory Conference Center to meet with scientists to discuss current research. GRIN disorders occur because of mutations in genes encoding NMDA receptors, which play key roles in memory, learning and neuronal development. NMDA receptors are a type of receptor for glutamate, the main excitatory neurotransmitter in the brain. The receptors themselves are encoded by multiple genes and assemble into tetramers. When their function is altered by mutations in one of these genes, symptoms appear in infancy or early childhood, usually including epilepsy and developmental delay.

The conference was the first time several patient advocacy groups oriented around GRIN-related disorders had met together, says Denise Rehner, president of the CureGRIN Foundation and mother of an affected child. For parents, this was an opportunity to connect with each other and advocacy groups, and to interact with scientists. For researchers, it was a chance to hear from those who are being impacted by their studies, and to discuss better ways to share data.

“We got a chance to explain to all the stakeholders – patient groups, foundations, companies – exactly what we do,” said Emory neuroscientist and conference organizer Stephen Traynelis, director of the Center for Functional Evaluation of Rare Variants. Traynelis and colleague Hongjie Yuan have been tracking the direct impacts of mutations on the function of the NMDA receptor. In doing so, they plan work with clinicians to compile registries, linking specific functional data to patient symptoms.

In addition to understanding underlying mechanisms and outcomes of GRIN disorders, researchers want to figure out how to treat affected children with existing drugs. Several options exist for targeting NMDA receptors, such as dextromethorphan (a cough suppressant) or memantine, approved for symptoms of Alzheimer’s. Traynelis and Yuan previously collaborated with the Undiagnosed Disease Program (now the Undiagnosed Disease Network) at the National Institutes of Health to investigate memantine as a treatment for a child with a GRIN2A mutation, showing that the drug could reduce seizure burden in one patient. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Rare inherited musculoskeletal disorder illustrates broader themes

More than fifteen years ago, Emory geneticist William Wilcox was a visiting professor in Montevideo, Uruguay. There he worked with local doctors, led by Roberto Quadrelli, to study a family whose male members appeared to have an X-linked inherited disorder involving heart disease and musculoskeletal deformities.

In March 2016, Wilcox and his colleagues reported in Circulation: Cardiovascular Genetics that they had identified the genetic mutation responsible for the disorder, called “Uruguay syndrome.” His former postdoc Yuan Xue, now a lab director at Fulgent Diagnostics and a course instructor in Emory’s genetics counseling program, was the lead author.

Wilcox_William_Genetics_22

William Wilcox, MD, PhD

“It took many years and advances in technology to move the molecular definition from localization on the X chromosome to a specific mutation,” Wilcox says.

Still, with current DNA sequencing technology, this kind of investigation and genetic discovery takes place all the time. Why focus on this particular paper or family?

*This gene is a big tent — Mutations in FHL1, the gene that is mutated in the Uruguayan family, are responsible for several types of inherited muscle disorders, which differ depending on the precise mutation. In 2013, an international workshop summarized current knowledge on this family of diseases.

Some forms of FHL1 mutation are more severe, such as reducing body myopathy, which can have early childhood onset leading to respiratory failure. Other forms are less severe. While some men in the Uruguayan family died early from heart disease, the man who Wilcox helped treat is now teaching high school and his hypertrophic cardiomyopathy is stable on a beta blocker.

“Studying a sample of his muscle proved that we had the right gene and some of what the mutation does,” Wilcox says.

*Studying rare mutations can lead to blockbuster drugs – The discovery of potent yet expensive cholesterol-lowering PCSK9 inhibitors, which grew out of the study of familial hypercholesterolemia, is a prominent example.

FHL1 regulates muscle growth by interacting with several other proteins. Probing its function may yield insights with implications for the treatment of muscular dystrophies and possibly for athletes. As NPR’s Jon Hamilton explains, the development of myostatin inhibitors, intended to help people with muscle-wasting diseases, has led to concern about them becoming the next generation of performance-enhancing drugs. Read more

Posted on by Quinn Eastman in Heart Leave a comment