To go along with the (new) Spring 2015 Emory Medicine magazine set of features on deep brain stimulation for depression, movement disorders and epilepsy, here is a fascinating 2013 case report from Emory neurosurgeon Robert Gross and colleagues. The first author is electrical engineer Otis Smart.
It’s an example of the kinds of insights that can be obtained from implantable electrical stimulation devices, which can record signals from seizures inside the brain over long periods of time (more than a year).
As the authors write, “the technology can record brain activity while the patient is in a more naturalistic environment than a hospital, becoming an invasive ambulatory EEG.†Read more
* its status as the most common inherited form of intellectual disability and a major single-gene cause of autism spectrum disorder (ASD)
*the importance of the RNA-binding protein FMRP as a regulator of synaptic plasticity in neurons
*the potential applicability of drugs developed for fragile X for other forms of ASD
Readers interested in neurodevelopment disorders may want to check out this Nature Reviews Drug Discovery piece, which chews over some setbacks in clinical research on fragile X. Emory researchers have a strong connection with the drug strategies used in the recent clinical trials, but have also been working on alternative approaches. Read more
Drug discovery veteran Dennis Liotta and his team continue to look for ways to fight against HIV. Working with pharmaceutical industry colleagues, he and graduate student Anthony Prosser have discovered compounds that are active against three different targets: immune cells’ entry gates for the virus (CCR5 and CXCR4), and the replication enzyme reverse transcriptase. That’s like one arrow hitting three bulls eyes. An advantage for these compounds: it could be less likely for viral resistance to develop.
For more, please go to the American Chemical Society — there will be a press conference from the ACS meeting in Denver on Monday, and live YouTube.
A risk calculator for cardiovascular disease, developed as a companion for the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, may account for racial differences in sub-clinical vascular function better than the Framingham Risk Score, Emory cardiology researchers say.
Their findings are scheduled for presentation Monday at the American College of Cardiology meeting in San Diego.
African Americans, especially men, tend to have a higher prevalence of cardiovascular disease, but this differences are not reflected in the Framingham Risk score. Arterial stiffness is a sign of heart disease risk that tends to appear more prominently among African Americans than whites. Cardiovascular research fellow Jia Shen, MD, MPH, and Emory colleagues analyzed data on arterial stiffness and structure from 1235 people – 777 whites and 458 African-Americans — enrolled in two large studies (Center for Health Discovery and Well Being and META-Health). Read more
MicroRNAs have emerged as important master regulators in cells, since each one can shut down several target genes. Riding on top of the master regulators is Drosha, the RNA-cutting enzyme that initiates microRNA processing in the nucleus. Drosha and its relative Dicer have been attracting attention in cancer biology, because they are thought to be behind a phenomenon where cancerous cells can “infect†their healthy neighbors via tiny membrane-clothed packets called exosomes.
At Emory, pharmacologist Zixu Mao and colleagues recently published in Molecular Cell their findings that Drosha is regulated by stress (experimentally: heat or peroxide) through p38 MAP kinase.
Our recent news item on Emory pathologist Keqiang Ye’s obesity-related research (Molecule from trees helps female mice only resist weight gain) understates how many disease models the proto-drug he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in. We do mention that Ye’s partners in Australia and Shanghai are applying to begin phase I clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.
The increasing clinical use of next generation sequencing in genetic testing, especially whole exome and whole genome, continues to be a hot topic. The ability to contribute to diagnosis, clinical utility, incidental findings and whether insurance will cover next-gen sequencing are all changing.
A Nature Medicine article lays out a lot of the emerging business issues on next-gen sequencing. On the topic of incidental findings, Buzzfeed science editor Virginia Hughes last week reported stories of women who receive a cancer diagnosis as a result of having a prenatal genetic test.
“These cases, though extremely rare, are raising ethical questions about the unregulated and rapidly evolving genetic-testing industry,” Buzzfeed says.
At a recent Department of Pediatrics seminar, Emory geneticist Michael Gambello described examples of how whole exome sequencing, performed to diagnose intellectual disability or developmental problems in a child, can uncover cancer or neurodegenerative disease risk mutations in a parent. The question becomes, whether to notify the parent for something that may or may not be actionable. This is why Emory Genetics Laboratory’s whole exome sequencing service has an extensive opt-in/opt-out consent process.
Emory Genetics Laboratory executive director Madhuri Hegde, working with the Association of Molecular Pathology, has been a leader in pushing genetic testing laboratories to adopt best practices. Read more
Everything is connected, especially in the brain. A protein called BAI1 involved in limiting the growth of brain tumors is also critical for spatial learning and memory, researchers have discovered.
Mice missing BAI1 have trouble learning and remembering where they have been. Because of the loss of BAI1, their neurons have changes in how they respond to electrical stimulation, and subtle alterations in parts of the cell needed for information processing.
Erwin Van Meir, PhD, and his colleagues at Winship Cancer Institute of Emory University have been studying BAI1 (brain-specific angiogenesis inhibitor 1) for several years. Part of the BAI1 protein can stop the growth of new blood vessels, which growing cancers need. Normally highly active in the brain, the BAI1 gene is lost or silenced in brain tumors, suggesting that it acts as a tumor suppressor.
The researchers were surprised to find that the brains of mice lacking the BAI1 gene looked normal anatomically. They didn’t develop tumors any faster than normal, and they didn’t have any alterations in their blood vessels, which the researchers had anticipated based on BAI1’s role in regulating blood vessel growth. What they did have was problems with spatial memory.
Neuroprotective drugs might seem impractical or improbable right now, after two big clinical trials testing progesterone in traumatic brain injury didn’t work out. But one close observer of drug discovery is predicting a “coming boom in brain medicines.” Maybe this research, which Emory scientists have been pursuing for a long time, will be part of it.
In the 1990s, neuroscientists identified a class of drugs that showed promise in the area of stroke. NMDA receptor antagonists could limit damage to the brain in animal models of stroke. But one problem complicated testing the drugs in a clinical setting: the side effects included disorientation and hallucinations.
Now researchers have found a potential path around this obstacle. The results were published in Neuron.
“We have found neuroprotective compounds that can limit damage to the brain during ischemia associated with stroke and other brain injuries, but have minimal side effects,†says senior author Stephen Traynelis, PhD, professor of pharmacology at Emory University School of Medicine.
“These compounds are most active when the pH is lowered by biochemical processes associated with injury of the surrounding tissue. This is a proof of concept study that shows this mechanism of action could potentially be exploited clinically in several conditions, such as stroke, traumatic brain injury and subarachnoid hemorrhage.†Read more
The importance of the SorLA or LR11 receptor in braking Alzheimer’s was originallydefined here at Emory by Jim Lah and Allan Levey’s labs. Japanese researchers recently determined the structure of SorLA and published the results in Nature Structural and Molecular Biology. Their findings point toward a direct role for SorLA in binding toxic circulating beta-amyloid and transporting it to the lysosome for degradation. Hat tip to Alzforum.
