Ahead of this week’s Morningside Center conference on repurposing drugs, we wanted to highlight a recent paper in NPJ Precision Oncology by dermatologist Jack Arbiser. It may represent a new chapter in the story of the beta-blocker propranolol.
Several years ago, doctors in France accidentally discovered that propranolol is effective against hemangiomas: bright red birthmarks made of extra blood vessels, which appear in infancy. Hemangiomas often don’t need treatment and regress naturally, but some can lead Read more
The results suggest that FK506 might be repurposed as a “stand-alone” replacement for recombinant BMP-2 (bone morphogenic protein 2). That product has been a huge commercial success for Medtronic, in the context of spinal fusion surgeries, although controversial because of cost and side effects.
BMP-2 is more potent gram for gram, but FK506 still may offer some opportunities in local delivery. From Sangadala et al (2019)
One of Willett’s co-authors is orthopedics chair Scott Boden, MD, whose lab previously developed a system to search for drugs that could enhance BMP-2. Previously, other researchers had observed that FK506 can enhance the action of BMP-2 – this makes sense because FK506’s target protein is a regulator of the BMP pathway. Willett’s team used FK506 on its own, delivered in a collagen sponge.
“That is the big finding here, that it has the potential to be used on its own without any BMP-2,” he says.
The sponge is a possible mechanism for getting the drug to tissues without having too many systemic effects. Willett’s lab is now working on refining delivery, dosing and toxicity, he says.
Willett, based at the Atlanta VA Medical Center, is in the Department of Orthopedics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. He and Sree Sangadala, PhD (first author of the IJMS paper) currently have a grant from National Center for Advancing Translational Sciences on this project.
An experimental screening method, developed by Emory and Georgia Tech scientists, aims to detect immune rejection of a transplanted organ earlier and without a biopsy needle.
The technology is based on nanoparticles that detect granzyme B enzymes produced by killer T cells. When the T cells are active, they slice up the nanoparticles, generating a fluorescent signal that is detectable in urine. The results from a mouse skin graft model were published in Nature Biomedical Engineering, from Gabe Kwong’s lab at GT and Andrew Adams’ at Emory. More extensive story here.
The National Institutes of Health has announced a five-year, $1.9 million Transformative Research Award to Emory virologist Edward Mocarski, PhD for his work on how the mechanisms of programmed cell death can be subverted.
Mocarski is Robert W. Woodruff professor of microbiology and immunology at Emory University School of Medicine and Emory Vaccine Center. His research, which originated in probing how cells commit suicide when taken over by viruses, could lead to advances in regenerative medicine and organ transplant.
Thomas Barker, PhD (left) and Edward Mocarski, PhD (right)
The grant, funded through the National Institute of Allergy and Infectious Diseases, is one of nineÂ â€œhigh-risk-, high-rewardâ€ Transformative Research Awards (13 recipients) announced by the NIH on October 6.
In the same group this year, Thomas Barker in the Wallace H. Coulter Department of Biomedical Engineering atÂ Georgia Tech and Emory University received a Transformative Research AwardÂ for his research on mechanosensors + pulmonary fibrosis.
When Jon Pomenville of Anderson, SC, decided to donate a kidney altruistically to someone â€“ anyonein need, anywhere in the country â€“ little did he know his selfless sacrifice would in turn change the lives of not one, but numerous individuals and their families, including one little boy from Atlanta.
And little did he know that the selfless, anonymous act would quickly become not so anonymous. During a recent post-surgical clinic visit to Emory University Hospital, Pomenville met by accident â€“ right in the transplant clinic waiting room â€“ many of the individuals whose lives were changed. Soon the patients â€“ recipients and donors â€“ two father and son combinations and Pomenville, the man who would give to anyone â€“ were hugging, shaking hands, and recounting their backgrounds and experiences.
Pomenville and the others, who were all part of what is called a paired kidney exchange, were unwittingly scheduled for appointments within a short period of one another. As one person began recounting the experience, eyes and ears began to focus on the tale being told from across a crowded room.
A chance meeting in a doctors’ waiting room led to a meeting between most of the people involved in the paired kidney exchange.
The Emory Transplant Center created and opened its innovative Paired Donor Kidney Exchange Program in 2009, providing greater hope for patients in need of kidney transplants. According to Kenneth Newell, MD, director of Emory’s living donor program, a paired exchange donation allows healthy individuals to donate a kidney to either a friend, loved one, or even altruistically to a stranger, despite incompatible blood matches. In paired donation, a donor and recipient are matched with another incompatible donor and recipient and the kidneys are exchanged between the pairs.
The procedure is another form of living donor transplantation. Donated kidneys also come from recently deceased donors. While most kidneys from deceased donors function well, studies have shown that a kidney from a living donor, either a blood relative or an unrelated person, provides the greatest chance for long-term success.
“Paired donor exchanges allow us to cast a much wider net to find compatible donors and recipients,” says Newell. “With a paired kidney transplant, one incompatible donor-pair is able to give a healthy kidney to a compatible recipient. In exchange, the second donor-recipient pair will give a compatible kidney to the first donor-recipient pair, making two compatible living donor transplants possible and increasing the potential number of available donor kidneys. This option can help those patients waiting for kidney transplants who have family members or friends willing to be donors and who are medically suitable, but who have an ABO blood type that is incompatible with the recipient’s blood type.”
Because of Pomenvilleâ€™s donation, a 7-year-old boy named Zion was able to receive a lifesaving kidney from an unrelated donor because his dad, Mike, was able to donate. His surgery took place at Children’s Healthcare of Atlanta at Egleston.
And Gerald Smith of Five Points, Ala., would receive his life-saving kidney because his son, Matt, a recent University of Alabama graduate, would donate his to Zion. And finally, 20 year-old Edward Hill of Macon, a young man with a history of health challenges, would also receive his transplant at Childrenâ€™s Healthcare of Atlanta â€“ completing the six-person cycle, although the donor of Edwardâ€™s kidney is still unknown.
And Zion and Matt Smith will not only share a common bond and connection throughout life in the form of a kidney, but something even sweeter that that â€¦ blue Powerade.
â€œIâ€™ve always really enjoyed drinking Powerade, particularly the blue flavor,â€ says Smith. Shortly after Zion awoke from his surgery, he inexplicably began requesting the blue-tinted soft drink too.
Other powerful kidney transplant stories out of Emory:
Nearly 45 years after she cared for Georgia’s first organ transplant recipient, Millie Elliott, 84, visited the Emory Transplant Center outpatient transplant clinic to see how things have changed since her time at Emory. Elliott, who was Millie Burns at the time, worked at Emory University Hospital first as an obstetrics nurse, then as head nurse of an NIH-sponsored clinical research unit at Emory from 1961 to 1967. She served as a dialysis nurse on that unit and may have been the Southeast’s first renal transplant coordinator.
During her recent visit to Emory, this former Cadet Nurse Corps nurse and World War II veteran regaled the transplant center staff and kidney transplant program director Thomas Pearson, MD, PhD, with her stories about the first transplant at Emory. Elliott recalled spending a lot of time researching medical sources to prepare herself and her nurses for that remarkable day. The first transplant patient was a 16-year -old boy with renal failure who received a donor kidney from his father.
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 â€œEdmonton protocolâ€ after pioneers at the University of Alberta. While the emergence of this method was a major step forward, there are limitations:
This weekend’s slate of racing at the Atlanta Motor Speedway, including the marquee Emory Healthcare 500 NASCAR Sprint Cup race Sunday night, will have a uniquely Emory flavor that exceeds far beyond just the naming rights for the event that will be watched by millions of fans around the country. Emory Healthcare is the official healthcare partner for the Atlanta Motor Speedway and this yearâ€™s Emory Healthcare 500 NASCAR Sprint Cup Series Race.
When Emory Healthcare and Atlanta Motor Speedway officials began searching for the grand marshal of this yearâ€™s Emory Healthcare 500 Sprint Cup Series race, they didnâ€™t have to search long or far to find the perfect candidate â€“ and one who already possessed the perfect tailor-made nickname for such an occasion.
Green first came to be known as â€œMr. 500â€ in March 2008, after he became the 500th heart transplant recipient at Emory University Hospital in Atlanta.
Keeping his motor running
Wayne Reese has been racing motocross and super late model cars on dirt tracks for more than 11 years, and he knows the risks. One risk he wonâ€™t take, however, is with his health.
Reese, a prostate cancer survivor, will be the Honorary Starter at the Emory Healthcare 500.Â In this role, Reese will drop the Green Flag to start the race.Â In addition, his son Brian will drive his Reese Motorsports Super Late Model Number 33 in the pre-race parade.
Reese, 55, recently completed therapy at Emory University Hospitalâ€™s Department of Radiation Oncology.Â He says he knew he wanted to be treated at Emory because his wife was treated at Emoryâ€™s Winship Cancer Institute.Â â€œWe appreciate all the help weâ€™ve gotten there.”
Reese recently demonstrated his appreciation by putting the Winship Cancer Institute of Emory University logo on his race cars.
Emory’s own pit crew
When more than 150,000 race fans, visitors and support crews flood Atlanta Motor Speedway this Labor Day weekend, they may learn a thing or two about their health â€“ possibly saving their own lives in the process.
Emory Healthcare will bring its own pit crew team of volunteers to Henry County this weekend to provide free health care screenings including:
â€¢Â Â Â Blood pressure screenings
â€¢Â Â Â Smoking cessation help and information
â€¢Â Â Â Head, neck and skin cancer screenings
â€¢Â Â Â Body Mass Index (BMI) screenings
â€¢Â Â Â General health and wellness information
â€œHaving this incredible opportunity to reach out to so many men and women to provide potentially life-saving cancer screenings, blood pressure checks, and informative ways to live a longer and healthier life, is a perfect way for us to thank those in our community who have allowed us to serve them over the years, while also supporting this special event that means so much to our region,” says Dane Peterson, chief operating officer for EmoryUniversity Hospital Midtown. “At the end of the day, we hope to make a difference in the lives of more than a few individuals and ensure that they will be able to return for many more exciting Labor Day weekends at the Atlanta Motor Speedway.â€
â€œOther 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 GRAâ€™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.
Encouraged by Emory’s success, Edmund Waller, MD, PhD, director of Emoryâ€™s Bone Marrow and Stem Cell Transplant Center says, “While 3,000 is a nice round number, it’s the middle of a growing and successful program. After 3,000 procedures, I know we all look forward to the future of this program.â€
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.