Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this Read more

Mother's milk is OK, even for the in-between babies

“Stop feeding him milk right away – just to be safe” was not what a new mother wanted to hear. The call came several days after Tamara Caspary gave birth to fraternal twins, a boy and a girl. She and husband David Katz were in the period of wonder and panic, both recovering and figuring out how to care for them. “A nurse called to ask how my son was doing,” says Caspary, a developmental Read more

Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

Allan Kirk

Catching up on Emory transplant advances

While preparing to discuss Ebola virology with Emory infectious disease specialist Aneesh Mehta next week, we noticed two recent research papers on which he is a co-author. Both have to do with organ transplantation, since Mehta is Assistant Director of Transplant Infectious Diseases.

Fecal microbiota transplantation for refractory Clostridium difficile colitis in solid organ transplant recipients

Fecal transplant is gaining ground as a remedy for C. difficile-driven diarrheal infections, which can appear in patients whose normal intestinal bacteria are wiped out by antibiotics. Fecal transplant has not been widely studied in organ transplant recipients, who must take drugs to keep their immune systems from rejecting the transplanted organ, because of concerns about infectious disease complications. This paper describes two patients, one a lung transplant recipient and one a kidney transplant recipient, who received fecal transplants to resolve their C. difficile diarrhea without complications. The lead authors are infectious disease specialists Rachel Friedman-Moraco and Colleen Kraft. Kraft has been a pioneer in this area of research.

Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors

Medical school dean Chris Larsen and Emory Transplant Center executive director Tom Pearson (both co-authors) were key members on the team that developed belatacept, a FDA-approved drug since 2011. Belatacept was designed to get away from the cruel paradox where a kidney recipient, to prevent transplant rejection, has to take calcineurin inhibitor drugs that slowly poison the kidney and cardiovascular health. Belatacept inhibits the immune response by a different mechanism. Yet transplant specialists have generally been cautious in moving toward a regimen that relies on it.

As reported in this paper, Emory transplant doctors took off the training wheels, aiming to get to the point where kidney transplant recipients are taking a once-a-month infusion of belatacept only. With some patients, it was possible to reach that goal, but not all. In fact, as the authors describe, some patients chose not to try to wean themselves off the other drugs, and doctors advised against the attempt for a handful. This clinical trial was also notable because some transplant recipients received immune-educational cells from their organ donors in the form of bone marrow.

The lead author, former Emory Transplant Center scientific director Allan Kirk, moved to Duke this spring.

Posted on by Quinn Eastman in Immunology Leave a comment

Emory transplant roundup

A recent Associated Press story highlighted clinical trials aimed at helping kidney transplant recipients give up their anti-rejection drugs:

The experimental approach: Transplant the seeds of a new immune system along with a new kidney. It’s the 21st-century version of a bone marrow transplant, and possible for now only if the transplanted kidney comes from a living donor.

How does it work? Doctors cull immune system-producing stem cells and other immunity cells from the donor’s bloodstream. They blast transplant patients with radiation and medications to wipe out part of their own bone marrow, far more grueling than a regular kidney transplant. That makes room for the donated cells to squeeze in and take root, creating a sort of hybrid immunity that scientists call chimerism, borrowing a page from mythology.

Emory Transplant Center scientific director Allan Kirk is leading a study that takes a similar approach, involving a depletion of the recipient’s immune cells and an infusion of bone marrow, which introduces new immune cells from the donor.

Allan Kirk, MD, PhD

Nature Medicine also has a good explanation of this area of research. Kirk is quoted in this recent story:

“The impetus to take the risk and pull people off immunosuppressants completely is lower now,” says Kirk… “It’s all about risk-benefit ratios and about making smart decisions with the tools we have—and we have a lot more tools now.”

Why go through so much trouble to avoid anti-rejection drugs? The most common drugs taken by transplant recipients, called calcineurin inhibitors, can reduce an individual’s ability to fight infections, lead to high blood pressure and high blood sugar and, ironically, tend to damage the kidney over time. Emory scientists played a major role in developing an alternative, belatacept, which was approved last year by the FDA.

Emory transplant surgeon Ken Newell was also mentioned in the AP story for his study of rare individuals who were able to go “cold turkey” and avoid having their immune systems reject their donated kidneys. One of these individuals, Lisa Robinson, had an interesting story to tell about how came to that point:

Three years after her kidney transplant, she found it hard to tolerate the side effects of the immunosuppressive drugs, which included swelling, weight gain and depression. On top of that, her creatinine levels were rising, indicating that her donated kidney was losing function. Without explicit approval from her doctor, she decided to taper off her drugs, first cyclosporine and then steroids.

“This turned out to be the right choice for me, but I’m not suggesting that others do what I did,” she says. “Everyone has to figure out what works for them. My main motivation was that I didn’t want to go through another kidney transplant.”

Based on data from Robinson and other people who had similar experiences, Newell has been able to identify a pattern of genes turned on in their immune cells that may predict whether someone could be able to become “tolerant.” Much of transplant biology focuses on one type of immune cell (T cells), but Newell found that the cells that may make the biggest difference for long-term tolerance are different, B cells. This makes sense because of B cells’ role in chronic rejection, Emory’s Stuart Knechtle has written.

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Challenges in islet transplantation

Two recent research papers from the Emory Transplant Center describe research on pancreatic islet transplantation, an experimental procedure that could help people with type I diabetes live without daily insulin injections.

Islet transplantation may offer people with type I diabetes the ability to produce their own insulin again

As with other types of transplantation, the challenge with islet transplantation is to avoid rejection of the donated organ and to balance that goal against side effects from the drugs needed to control the immune system. These papers illustrate how that balancing act is especially complex.

In the last decade, transplant specialists developed a method for islet transplantation named the “Edmonton protocol” after pioneers at the University of Alberta. While the emergence of this method was a major step forward, there are limitations:

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Posted on by Quinn Eastman in Uncategorized 3 Comments

GRA partnership promotes research collaboration, grows economy

“Other states wish they had what Georgia has: Research universities that work together, and a unified commitment from industry, government and academia to grow a technology-based economy,” states Michael Cassidy, president and CEO of the Georgia Research Alliance (GRA) in the GRA’s recent annual report.”

As one of six GRA universities, Emory has benefited from this unique partnership in numerous ways: through its 11 Eminent Scholars, multidisciplinary university and industry collaborations, and support for research in vaccines, nanomedicine, transplantation, neurosciences, pediatrics, biomedical engineering, clinical research, and drug discovery.

Emory is featured throughout the report, including

  • The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory and its four eminent scholars, Xiaoping Hu, PhD, Eberhard Voit, PhD, Barbara Boyan, PhD and Don Giddens, PhD.
  • Emory transplant medicine expert and GRA Eminent Scholar Allan Kirk, MD, PhD, who collaborates with Andrew Mellor, PhD at the Medical College of Georgia on research to find enzymes that could keep the body from rejecting newly transplanted organs.
  • The Emory-University of Georgia Influenza Center of Excellence and its leading collaborators, GRA Eminent Scholar and Emory Vaccine Center Director Rafi Ahmed, PhD, and Emory microbiologist Richard Compans, PhD, along with UGA GRA Eminent Scholar Ralph Tripp.
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Pig stem cells: hope for Type 1 diabetes treatment

University of Georgia researchers recently reported on their work to create pigs with induced pluripotent stem cells. This type of cell, first developed about five years ago, has the ability to turn into any other kind of cell in the body.

An Emory transplant team, working with the UGA group, hopes to use this technology to develop pig islet cells as an alternative to human islets to treat patients with Type 1 diabetes. Type 1 diabetes usually occurs early in life and affects more than one million Americans who are unable to manufacture their own insulin because their pancreatic islets do not function.

Emory islet transplant team

The Emory Transplant Center has conducted clinical trials since 2003 transplanting human pancreatic islet cells into patients with Type I diabetes. Some of these patients have been able to give up insulin injections, either temporarily or permanently. Other sources of islets are needed for transplant though because of the large number of potential patients and because each transplant typically requires islets from several pancreases.

To create pigs using pluripotent stem cells, the UGA team injected new genes into pig bone marrow cells to reprogram the cells into functioning like embryonic stem cells. The resulting pluripotent cells were inserted into blastocysts (developing embryos), and the embryos were implanted into surrogate mothers. The resulting pigs had cells from the stem cell lines as well as the embryo donor in multiple tissue types.

The pluripotent stem cell process could allow researchers to make genetic changes to dampen or potentially eliminate the rejection of the pig islets by the human immune system.

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Tailoring transplant drugs for children

For adult organ transplant recipients, juggling a lifetime regimen of immunosuppressant drugs is difficult enough, but for children it presents an even greater challenge.  These drugs, which also can have toxic side effects, must strike a delicate balance between preventing organ rejection and protecting from infections.

But children’s immune systems are still “learning” what distinguishes them from the world around them, and children are constantly developing and changing, both physically and emotionally. This puts them at greater risk for complications either through inappropriate medication or failure to take these drugs properly.

A grant from the National Institute of Allergy and Infectious Diseases (NIAID), through the American Recovery and Reinvestment Act (ARRA), will support new studies at Emory University and Children’s Healthcare of Atlanta to help clinicians tailor therapies specifically for children receiving transplants.  The project will include hiring of additional personnel to undertake these studies.

Allan D. Kirk, MD, PhD, is principal investigator of the project, which is supported by a two-year grant of nearly $1.65 million. Kirk is professor of surgery and pediatrics in Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. He also is vice chair of research in the Department of Surgery and scientific director of the Emory Transplant Center.

The ARRA-funded project will not only help determine which medications children should take, but also will give them the support to care for their transplanted organs.  The Emory scientists are studying new biological monitoring technologies that can identify unique ways to determine exactly how much medication a child really needs. These studies are being combined with a novel transition care clinic specializing in helping children cope with their illness and assuming responsibility for their care.

“This award indicates exceptional insight by the NIAID into the critical link between a child’s physical well-being and their emotional maturity,” says Kirk. “It will accelerate progress in this vital area of research for a very deserving subset of chronically ill children.”

Posted on by Holly Korschun in Uncategorized 1 Comment