Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

IMSD program nurtures young scientists

The IMSD (Initiative to Maximize Student Development) program nurtures and mentors a diverse group of young scientists at Read more

Flu meeting at Emory next week

We are looking forward to the “Immunology and Evolution of Influenza” symposium next week (Thursday the 25th and Friday the Read more

How race + TBI experience affect views of informed consent

The upcoming HBO movie of The Immortal Life of Henrietta Lacks reminds us that biomedical research has a complex legacy, when it comes to informed consent and people of color.

A paper from Emory investigators, published in AJOB Empirical Bioethicstouches on related current issues. The paper examines how race and close experience with traumatic brain injury affect study participants’ views of informed consent in clinical research.

This emerged from a study of community consultation for EFIC (exception from informed consent), in connection with a nationwide clinical trial of progesterone for traumatic brain injury (TBI). EFIC describes clinical research performed when the normal process of obtaining patients’ informed consent is not possible, because of emergency conditions such as seizures or TBI. Before such studies can be undertaken, the FDA calls for protective procedures and community consultation.

In this case, researchers surveyed 2612 people at 12 sites involved in the TBI study. The survey asked about attitudes toward the EFIC aspects of the study and also asked if they had personal experience with traumatic brain injury – either themselves or someone close to them. How that personal connection affected their responses was influenced by race.

Key paragraph from discussion:

Among white participants, increased levels of acceptance of EFIC were found among those with any connections to TBI. On the other hand, among participants identifying as black or other nonwhite races, there was decreased acceptance of EFIC enrollment among TBI patients and no increase in acceptance among those with a family member/loved one with TBI. The fact that black and white participants with no personal TBI experience or with a more distant connection to TBI had similar acceptance rates suggests that baseline acceptance of EFIC among these two groups is fairly similar and that the experience with the condition itself plays a role in driving the observed differences…

Read more

Posted on by Quinn Eastman in Heart, Neuro, Uncategorized Leave a comment

Fecal transplant replants microbial garden

When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.

In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.

C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.

At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.

Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more

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Meningitis bacteria adapt to STI niche — again?

A new paper in PNAS from Emory scientists highlights a neat example of bacterial evolution and adaptation related to sexually transmitted infections. Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, sometimes appears in the news because of cases on college campuses or other outbreaks.

The N meningitidis bacteria causing a recent cluster of sexually transmitted infections in Columbus, Ohio and other US cities have adapted to the urogenital environment, an analysis of their DNA shows.

Update: May 2016 Clinical Infectious Diseases paper on the same urethritis cluster.

Genetic changes make this clade look more like relatives that are known to cause gonorrhea. Some good news is that these guys are less likely to cause meningitis because they have lost their outer capsule. They have also gained enzymes that help them live in low oxygen.

The DNA analysis helps doctors track the spread of this type of bacteria and anticipate which vaccines might be protective against it. Thankfully, no alarming antibiotic resistance markers are present (yet) and currently available vaccines may be helpful. Full press release here, and information about meningococcal disease from the CDC here.

This looks like a well-worn path in bacterial evolution, since N. gonorrhoeae is thought to have evolved from N. meningitidis and there are recent independent examples of N. meningitidis adapting to the urogenital environment. 

Posted on by Quinn Eastman in Immunology Leave a comment

To explain cancer biology, use metaphors

Using metaphors to explain biomedical concepts is our bread and butter. That’s why we were tickled to see a recent paper from Winship Cancer Institute bioethicist Rebecca Pentz and colleagues, titled:

Using Metaphors to Explain Molecular Testing to Cancer Patients

Pentz’s team systematically evaluated something that science writers and journalists try to do all the time (and not always well). And they did so with actual conversations between doctors and patients at Winship. The first author of the paper, published in The Oncologist, was medical student Ana Pinheiro.

The researchers studied 66 conversations with nine oncologists. In 25 of those conversations, patients reported that they were able to hear a metaphor. Here’s one example:

“We try to figure out what food makes this kind of cancer grow. For this cancer, the food was estrogen and progesterone. So we’re going to focus on blocking the hormones, because that way we starve the cancer of its food.”

The paper lists all 17 (bus driver, boss, switch, battery, circuit, broken light switch, gas pedal, key turning off an engine, key opening a lock, food for growth, satellite and antenna, interstate, alternate circuit, traffic jam, blueprint, room names, Florida citrus) and how they were used to explain eight cancer-related molecular testing terms.

When patients were asked about the helpfulness of a metaphor that was used, 85 percent of the time they demonstrated understanding and said it was helpful. So let the metaphors fly!

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Enhanced verbal abilities in the congenitally blind

A recent paper in Experimental Brain Research from Emory neuroscientist Krish Sathian and colleagues demonstrates that congenitally blind study participants displayed superior verbal, but not spatial abilities, when compared to their sighted counterparts. This may reflect both greater reliance on verbal information, and the recruitment of the visual cortex for verbal tasks.

Sathian’s team has also been investigating, through brain imaging studies, whether the visual cortex is involved in the processing of metaphors (2016 SFN abstract) in the congenitally blind. They previously showed that blind study participants were better at identifying rotated objects by touch. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Three remarkable Emory case reports from #ACC17

The big news from the American College of Cardiology meeting today is about PCSK9 inhibitors, which were known to be effective at lowering LDL cholesterol, and how much they really prevent heart attacks and save lives.

Lab Land went looking off the beaten path for individual stories of Emory cardiologists saving lives and was pleased to find several. We highlight here three remarkable case reports that are being presented at the ACC meeting. We look forward to learning more about these cases.

Refractory electrical storm 

Electrical storm is life threatening and refers to a recurrent arrhythmia. The arrhythmia did not respond to drug treatment, so anesthesiologists were brought in to perform left stellate ganglion block, an injection of medication into a nerve bundle in the neck, allowing diagnosis and further treatment. It turns out the arrhythmia was caused by sarcoidosis, a rare intrusion of immune cells into the heart. [Saturday morning: Michael Lloyd, Boris Spektor]

Hormone-producing tumor + cardiomyopathy 

A 30-year old woman came to doctors with drastically impaired heart function, although she did not have a blockage of her coronary arteries or signs of damage to the heart muscle. Doctors discovered a tumor near her spine that was producing heart-distorting hormones such as epinephrine. She underwent surgery to remove the tumor. [Saturday afternoon: Stamatios Lerakis]

Giving birth unveils birth defects

Ten days after giving birth, a woman came to a hospital with chest pain. Upon cardiac catheterization, a rearrangement of her coronary arteries was discovered. It appears that the congenital defect had gone undetected until the stress of giving birth. Under medical treatment, she is asymptomatic, but she will need future monitoring and possibly a procedure to correct the artery problems. [Sunday morning: Camden Hebson]

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Anti-TNF vs Alzheimer’s mouse model

An experimental anti-inflammatory drug has positive effects on neuron function and amyloid plaques in a mouse model of Alzheimer’s disease, Emory neuroscientists report. The findings are published in the journal Neurobiology of Disease.

Inflammation’s presence in Alzheimer’s is well established, but it is usually thought of as an accelerator, rather than an initiating cause. While everybody argues about the amyloid hypothesis, there’s a case to be made for intervening against the inflammation. Exactly how is an open question.

The drug tested, called XPro1595, targets the inflammatory signaling molecule tumor necrosis factor (TNF). Commercialized drugs such as etanercept and infliximab, used to treat autoimmune diseases, also block TNF. However, XPro1595 only interferes with the soluble form of TNF and is supposed to have less of an effect on overall immune function.

Senior author Malu Tansey (pictured) and her colleagues say that interfering with TNF could have direct effects on neurons, as well as indirect effects on the immune cells infiltrating the brain. They write that “the most promising finding in our study” is the ability of XPro1595 to restore long-term potentiation or LTP, which is impaired in the Alzheimer’s model mice. Read more

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Excellent exosomes harvest cardiac regenerative capacity

Thanks to biomedical engineer Mike Davis for writing an explanation of “Exosomes: what do we love so much about them?” for Circulation Research, a companion to his lab’s November 2016 publication analyzing exosomes secreted by human cardiac progenitor cells.

We can think of exosomes as tiny packages that cells send each other. They’re secreted bubbles containing proteins and regulatory RNAs. Thus, they may be a way to harvest the regenerative capacity of pediatric heart tissue without delivering the cells themselves.

Mike Davis, PhD is director of the Children’s Heart Research and Outcomes Center (HeRO), part of the Emory/Children’s/Georgia Tech Pediatric Research Alliance

Davis’ lab studied cardiac tissue derived from children of different ages undergoing surgery for congenital heart defects. The scientists isolated exosomes from the cardiac progenitor cells, and tested their regenerative activity in rats with injured hearts.

They found that exosomes derived from older children’s cells were only reparative if they were subjected to hypoxic conditions (lack of oxygen), while exosomes from newborns’  cells improved rats’  cardiac function with or without hypoxia. Read more

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Revived T cells still need fuel

Cancer immunotherapy drugs blocking the PD-1 pathway – known as checkpoint inhibitors – are now FDA-approved for melanoma, lung cancer and several other types of cancer. These drugs are often described as “releasing the brakes” on dysfunctional T cells.

A new study from Emory Vaccine Center and Winship Cancer Institute researchers shows that even if the PD-1-imposed brakes are released, the tumor-specific T cells still need “fuel” to expand in numbers and restore effective immune responses. That fuel comes from co-stimulation through a molecule called CD28.

The results were published Thursday by the journal Science.

Despite the success of PD-1-targeting drugs, many patients’ tumors do not respond to them. The study’s findings indicate that CD28’s presence on T cells could be a clinical biomarker capable of predicting whether drugs targeting PD-1 will be effective. In addition, the requirement for CD28 suggests that co-stimulation may be missing for some patients, which could guide the design of combination therapies.

For the rest of our press release and quotes from authors Rafi Ahmed, Alice Kamphorst and Suresh Ramalingam, please go here. For some additional links and thoughts on PD-1 and CD28, read on:

Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Direct reprogramming into endothelial cells

Direct reprogramming has become a trend in the regenerative medicine field. It means taking readily available cells, such as skin cells or blood cells, and converting them into cells that researchers want for therapeutic purposes, skipping the stem cell stage.

In a way, this approach follows in Nobel Prize winner Shinya Yamanaka’s footsteps, but it also tunnels under the mountain he climbed. Direct reprogramming has been achieved for target cell types such as neurons and insulin-producing beta cells.

Young-sup Yoon, MD, PhD

In Circulation Research, Emory stem cell biologist Young-sup Yoon, MD, PhD and colleagues recently reported converting human skin fibroblast cells into endothelial cells, which line and maintain the health of blood vessels.

Once reprogrammed, a patient’s own cells could potentially be used to treat conditions such as peripheral artery disease, or to form vascular grafts. Exactly how reprogrammed cells should be deployed clinically still needs to be worked out.

In cardiovascular disease, many clinical trials have been performed using bone marrow cells that were not reprogrammed. Emory readers may be familiar with studies conducted by Arshed Quyyumi, MD and colleagues, in which treatment was delivered after patients’ heart attacks. In those studies, sorted progenitor cells, some of which could become endothelial cells, were introduced into the heart. To provide the observed effects, the introduced cells were more likely supplying supportive growth factors.

In contrast, Yoon’s team is able to produce cells that already have endothelial character hammered into them. The authors have applied for a patent. The co-first authors were instructor Sang-Ho Lee, PhD and Changwon Park, PhD, assistant professor of pediatrics. Read more

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