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
In the prostate cancer field, there has been a push to move beyond PSA testing. With urine tests, it may be possible to avoid biopsies for men with suspected prostate cancer.
Martin Sanda, MD is chair of urology and leads Winship’s prostate cancer program
With PSA testing to guide decisions, only one in five men is found via biopsy to have a cancer that is sufficiently aggressive (Gleason score of 7 or higher) to warrant treatment right away.
A recently published paper in JAMA Oncology from urologist Martin Sanda and colleagues in the NCI’s Early Detection Research Network shows the potential of urine testing. Sanda’s team reports that two prostate cancer RNA biomarkers detectable in urine (PCA3 and T2:ERG) could be combined to enhance their discriminatory power and reduce unnecessary biopsies by almost half.
Keqiang Ye’s lab at Emory recently published a paper in Nature Communications that offers a two for one deal in Alzheimer’s drug discovery.
Periodically we hear suggestions that the amyloid hypothesis, the basis of much research on Alzheimer’s disease, is in trouble. Beta-amyloid is a toxic protein fragment that accumulates in extracellular brain plaques in Alzheimer’s, and genetics for early-onset Alzheimer’s point to a driver role for amyloid too.
In mice, inhibiting AEP hits two targets (amyloid and tau) with one shot
Unfortunately, anti-amyloid agents (either antibodies that sop up beta-amyloid or drugs that steer the body toward making less of it) have not shown clear positive effects in clinical trials.
That may be because the clinical trials started too late or the drugs weren’t dosed/delivered right, but there is a third possibility: modifying amyloid by itself is not enough.
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
As described in this 2016 JCI Insight paper, Emory and University of Toronto investigators wanted to do the opposite. They were aiming to develop antibody tools for studying and manipulating plasma cells, which are the immune system’s weapons factories, where antibody production takes place. The situation is flipped when we’re talking about antibodies. Here, the goal is to stand out.
Do these guys look like good spies?
Monoclonal antibodies are classic biomedical tools (and important anticancer drugs). But it’s tricky to develop antibodies against the places where antibodies themselves are made, because of the way the immune system develops. To guard against autoimmune disease, antibodies that would react against substances in the body are often edited out.
To get around this obstacle, researchers used organisms that have very different immune systems from humans: lampreys. Emory’s Max Cooper and colleagues had already shown how lampreys have molecules — variable lymphocyte receptors or VLRs — that function like antibodies, but don’t look like them, in terms of their molecular structure.
From the paper:
We reasoned that the unique protein architecture of VLR Abs and the great evolutionary distance between lampreys and humans would allow the production of novel VLRB Abs against biomedically relevant antigens against which conventional Abs are not readily produced because of structural or tolerogenic constraints.
How should doctors measure how messed up someoneâ€™s intestinal microbiome is?
This is the topic of a recent paper in American Journal of Infection Controlfrom Colleen Kraft and colleagues from Emory and the Centers for Disease Control and Prevention. The corresponding author is epidemiologist Alison Laufer Halpin at the CDC.
What the authors are moving towards is similar to Shannonâ€™s index, which ecologists use to measure diversity of species. Another way to think about it is like the Gini coefficient, a measure of economic inequality in a country. If there are many kinds of bacteria living in someoneâ€™s body, the disruption index should be low. If there is just one dominant type of bacteria, the disruption index should be high.
In the paper, the authors examined samples from eight patients in a long-term acute care hospital (Wesley Woods) who had recently developed diarrhea. Using DNA sequencing, they determined what types of bacteria were present in patients’ stool. The patientsâ€™ samples were compared with those from two fecal microbial transplant donors. Read more
In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found.Â One oxygen-shy type of bacteria that grows in the wound-healing environment,Â Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal andÂ human obesity.
An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.
The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.
The results were published on January 27 inÂ Nature Microbiology.Â Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.
â€œThis is a situation resembling recovery after a forest fire,â€ says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. â€œOnce the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.â€ Read more
To prevent auto-immune attack, our bodies avoid making antibodies against molecules found on our own cells. That leaves gaps in our immune defenses bacteria could exploit. Some of those gaps are filled by galectins, a family of proteins whose anti-bacterial properties were identified by Emory scientists.
In the accompanying video, Sean Stowell, MD, PhD and colleagues explain how galectins can be compared to sheep dogs, which are vigilant in protecting our cells (sheep) against bacteria that may try to disguise themselves (wolves).
The video was produced to showcase the breadth of research being conducted within Emoryâ€™s Antibiotic Resistance Center. Because of their ability to selectively target some kinds of bacteria, galectins could potentially be used as antibiotics to treat infections without wiping out all the bacteria in the body. Read more