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It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball,Â I corralledÂ them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developingÂ a variety ofÂ approaches to cardiac cell therapy.
2. Mobilizing the body’s own regenerative potential
Ahsan Husain’s work on how young hearts grow. Shan Ping Yu’s lab usingÂ parathyroid hormone boneÂ drug to mobilize cells for stroke treatment.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can passÂ blood-brain barrier).
5. Personal genomics/exome sequencing
6. Neurosurgeons, likeÂ Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patientsÂ fighting glioblastoma.
8. The hypersomnia field is waking up
Our Web expert tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
Posted on January 7, 2015 by
Patients who receive more cells get significant benefits. That’s a key lesson emerging from a clinical trial that was reported this week at the American Heart Association meeting in Chicago.
In this study, doctors treated heart attack patients with their own bone marrow cells, selected for their healing potential and then reinjected into the heart, in an effort to improve the heart’s recovery. In the PreSERVE-AMI phase II trial, physicians from 60 sites (author list) treated 161 patients, making the study one of the largest to assess cell therapy for heart attacks in the United States. The study was sponsored by NeoStem, Inc.
“This was an enormous undertaking, one that broke new ground in terms of assessing cell therapy rigorously,” says the study’s principal investigator, Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine and co-director of the Emory Clinical Cardiovascular Research Institute. “We made some real progress in determining the cell type and doses that can benefit patients, in a group for whom the risks of progression to heart failure are high.” Read more
Posted on November 21, 2014 by
Cardiologist Bob Taylor and colleagues have a new paper in PLOS One this week, looking at the biomechanical forces behind plaque erosion.
Plaque erosion is a mechanism for blood clots formation in coronary arteries that is not as well-understood as its more explosive counterpart, plaque rupture. Plaque erosion disproportionally affects women more than men and is thought to account for most heart attacks in younger women (women younger than 50).
“We believe that this work has implications for our better understanding of the underlying biology of coronary artery disease in women,” Taylor says. The first author of the paper is biomedical engineering graduate student Ian Campbell, who now has his PhD. The team collaborated with cardiovascular pathologist Renu Virmani in Maryland.
Cardiologists have well-developed ideas for how plaque rupture works*; see the concept of vulnerable plaque. Cholesterol and inflammatory cells build up in the coronary arteries over several years. At one point in a particular artery, the plaque has a core of dying inflammatory cells, covered by a fibrous cap. If the cap is thin (the patterns of blood flows near the cap influence this), there is a risk that the cap will break and the contents of the core will spill out, triggering a blood clot nearby.
Plaque erosion is more mysterious and can occur more gradually, the researchers have found. Read more
Posted on November 3, 2014 by
Exosomes are tiny membrane-wrapped bags, which form inside cells and are then spat out. Theyâ€™re about 100 or 150 nanometers in diameter. Thatâ€™s smaller than the smallest bacteria, and about as large as a single influenza or HIV virion. Theyâ€™re not visible under a light microscope, but are detectable with an electron microscope.
Scientific interestÂ in exosomes shot up after it was discovered that they can contain RNA, specifically microRNAs, which inhibit the activity of other genes. This could be another way in which cells talk to each other long-distance, besides secreting proteins or hormones. Exosomes are thus something like viruses, without the infectivity.
Since researchers are finding that microRNAs have potential as therapeutic agents, why not harness the vehicles that cells use to send microRNAs to each other? Similarly, if so much evidence points toward the main effect of cell therapy coming from what the cells make rather than the cells themselves, why not simply harvest what the cells make? Read more
Posted on September 9, 2014 by
If someone living in America and eating a typical diet and leading a sedentary lifestyleÂ lets a few years go by, we can expect plaques of cholesterol and inflammatory cells to build up in his or her arteries. We’re not talking “Super-size Me” here, we’re just talking average American. But then let’s say that same person decides: “OK, I’m going to shape up. I’m going to eat healthierÂ and exercise more.”
Let’s leave asideÂ whether low-carb or low-fat is best, and let’s say that person succeeds in sticking to his or her declared goals. How “locked in” are the changes in the blood vesselsÂ when someone has healthy or unhealthy blood flow patterns?
Biomedical engineer Hanjoong Jo and his colleagues published aÂ paper in Journal of Clinical Investigation that touches on this issue. They have an animal model where disturbed blood flow triggers the accumulation of atherosclerosis. They show that the gene expression changes in endothelial cells, which line blood vessels, have an epigenetic component.Â Specifically, the durable DNA modification known asÂ methylation is involved, and blocking DNA methylation with a drug used for treating some forms of cancer can prevent atherosclerosis in their model.Â This suggests that blood vessels retain an epigenetic imprint reflecting the blood flow patterns they see.
Although treating atherosclerosis with theÂ drug decitabine is notÂ a viable option clinically, Jo’s team was able to find severalÂ genes that are silenced by disturbed blood flow and that need DNA methylation to stay shut off. A handful of thoseÂ genes have aÂ common mechanism of regulationÂ and may be good therapeutic targets for drug discovery.
Posted on June 24, 2014 by
The entire heart muscle in young children may hold untapped potential for regeneration, new research suggests.
For decades, scientists believed that after a child’s first few days of life, cardiac muscle cells did not divide. Instead, the assumption was that the heart could only grow by having the muscle cells become larger.
CracksÂ were alreadyÂ appearingÂ in that theory. But new findings in mice, published May 8 inÂ Cell, provide a dramatic counterexample — with implications for the treatment of congenital heart disorders in humans. Read more
Posted on May 19, 2014 by
Stem cell therapy for heart disease is happening. Around the world, thousands of heart disease patients have been treated in clinical studies with some form of bone marrow cells or stem cells. But in many of those studies, the actual impact on heart function was modest or inconsistent. One reason is that most of the cells either donâ€™t stay in the heart or die soon after being introduced into the body.
Cardiology researchers at Emory have a solution for this problem. The researchers package stem cells in a capsule made of alginate, a gel-like substance. Once packaged, the cells stay put, releasing their healing factors over time.
Researchers used encapsulated mesenchymal stem cells to form a â€œpatchâ€ that was applied to the hearts of rats after a heart attack. Compared with animals treated with naked cells (or with nothing), rats treated with the capsule patches displayed increased heart function, reduced scar size and more growth of new blood vessels a month later. In addition, many more of the encapsulated cells stayed alive. Read more
Posted on October 11, 2013 by
Pure cardiac muscle cells, ready to transplant into a patient affected by heart disease.
Thatâ€™s a goal for many cardiology researchers working with stem cells. Having a pure population of cardiac muscle cells is essential for avoiding tumor formation after transplantation, but has been technically challenging.
Researchers at Emory and Georgia Tech have developed a method for Cheap Oakleys purifying cardiac muscle cells from stem cell cultures using molecular beacons.
Molecular beacons are tiny “instruments” that become fluorescent only when they find cells that have turned on certain genes. In this case, they target instructions to make a type of myosin, a protein found in cardiac muscle cells.
Doctors could use purified cardiac muscle cells to heal damaged areas of the heart in patients affected by heart attack and heart failure. In addition, the molecular beacons technique http://www.lependart.com could have broad applications across regenerative medicine, because it could be used with other types of cells produced from stem cell cultures, such as brain cells or insulin-producing islet cells.
The results are published in the journal Circulation.
“Often, we want to generate a particular cell population from stem cells for introduction into patients,” says co-senior author Young-sup Yoon, MD, PhD, professor of medicine (cardiology) and director of stem cell biology at Emory University School of Medicine. “But the desired cells often lack a readily accessible surface marker, or that marker is not specific enough, as is the case for cardiac muscle cells. This technique could allow us to purify almost any type of cell.”
Posted on September 5, 2013 by
Who should get stents, the tiny metal tubes designed to keep clogged coronary arteries open? Someone who is having a heart attack certainly should, and the life-prolonging benefits have been demonstrated in several studies. But results have been more ambiguous for patients who have “stable angina”: chest pain that comes with exertion but goes away at rest.
A recent study addressing this topic called FAME 2 has received extensive media coverage. It was published in the New England Journal of Medicine and also presented at the European Society of Cardiology meeting in Munich. Kreton Mavromatis, MD, director of cardiac catheterization at the Atlanta VA Medical Center and assistant professor of medicine at Emory, was a co-author on the NEJM paper.
In the new study, researchers used a technique called fractional flow reserve (FFR) to decide if someone with stable angina should get a stent, or receive medical therapy with drugs such as aspirin and statins. Conventionally, X-ray coronary angiography is used to assess the need for a stent.
FFR involves introducing a pressure sensor via guidewire into the coronary artery, to measure how much blood flow is being blocked. FAME 2 was sponsored by St Jude Medical, a company that makes guidewire equipment for use in FFR.
The clinical trial was stopped early because of clear differences in the rates of hospitalization (4 percent for stents against 13 percent for medical therapy)
“FAME 2 showed that the strategy of treating stable ischemic heart disease with FFR-guided coronary stenting reduces the combination of death, MI and urgent revascularization as compared with strategy of medical therapy alone,” Mavromatis says. “This benefit was specifically due to the reduced need of urgent revascularization due to acute coronary syndrome, a dramatic event for our patients.”
“It is important to recognize that less symptoms of angina and less chance of hospitalization are tremendous benefits that our patients really appreciate,” Mavromatis says. “I think FFR will play a bigger role in evaluating and treating coronary artery disease, as it can direct stenting much more precisely than angiography toward clinically important coronary artery disease, improving patients’ outcomes and saving money.”
The FFR procedure costs several hundred dollars but that is significantly less than the cost of implanting a coronary stent. Habib Samady, MD, director of interventional cardiology at Emory, has also been an advocate for the use of FFR to select who would benefit from a coronary stent. He wrote an article describing its uses in 2009:
We have been using and advocating FFR since pressure guidewire technology first came to the U.S. in 1998. At Emory, we are sometimes asked to reevaluate patients who have been slated for CABG surgery at another hospital where recommendations are made based on angiography alone. When we evaluate these cases using FFR, we are sometimes able to recommend courses of treatment that involve fewer stents or even medical therapy. Occasionally, based on FFR data, we send our patients for an endoscopic or “minimally invasive” bypass and stent the remaining narrowings.
In addition, FFR has helped reduce the number of multi-vessel PCIs performed. Patients who might have received stents in three vessels after angiography alone would likely receive stents in only one or two vessels after FFR-guided analysis. Among patients with single-vessel disease, FFR often has allowed us to recommend medical treatment in lieu of stenting. Implanting fewer stents also means using less contrast agent and fewer materials, which lowers the expenses involved in treatment.
A large, multi-center study called ISCHEMIA is starting that will address the coronary stent vs medical therapy issue in a more definitive way. Both Emory and the Atlanta VA Medical Center are participating. “This is a very important next step in understanding the benefits of invasive therapy of stable ischemic heart disease,” Mavromatis says.
Posted on September 7, 2012 by
A story in yesterdayâ€™s edition of the Washington Post claims that many Americans have poor health literacy. The Post cited a 2006 study by the U.S. Department of Education that found that 36 percent of adults have only basic or below-basic skills for dealing with health material. According to the report, this means about 90 million Americans can understand discharge instructions written only at a fifth-grade level or lower.
Emory Healthcare heart transplant cardiologist, Javed Butler, MD, MPH, was included in yesterday’s Post article citing his experience with patients who have health literacy issues. “When we say ‘diet,’ we mean ‘food,’ but patients think we mean going on a diet,” said Butler. “And when we say ‘exercise,’ we may mean ‘walking,’ but patients think we mean ‘going to the gym.’ At every step there’s a potential for misunderstanding.”
Butler, a professor of medicine at the Emory School of Medicine and director of Heart Failure Research for Emory Healthcare is studying this issue and its impact on patients with heart failure. He recently reported some of his findings Nov. 17 at the American Heart Association Scientific Sessions conference in Chicago.
To read the entire Washington Post story, please click here.
Posted on March 2, 2011 by