This past year, the School of Medicine rolled out a new five-year research strategic plan and looked back at progress over the past two decades to gain insight into directions for the future. From 1989 to 2009, the school had a 10-fold increase in NIH research funding. Almost every year since the mid-1990s, the school has been either the first- or second-fastest rising recipient of NIH dollars. And today its ratio of impactful scientists—those cited frequently in the literature and those whose discoveries have made them “gamechangers,” as a new recognition program calls them—is dense in relation to the relatively small size (450) of its research faculty.
Brain disorders - This past year, Emory researchers identified a new class of compounds that alter the function of NMDA receptors, critical players in communication between brain cells. This work may lead to new drug treatments for schizophrenia, Parkinson’s, and other disorders. Blocking one variety of NMDA receptor to mitigate brain damage from stroke is the focus of NeurOp, one of more than 50 start-up companies Emory has launched since the 1990s to move drug discovery toward clinical use. NeurOp recently announced a two-year research collaboration with Bristol-Myers Squibb.
Improved transplant drugs - This past summer, Emory clinician-scientists learned of long-awaited FDA approval of the drug Nulojix (belatacept) for prevention of graft rejection after kidney transplants. This is the first time a new class of drugs has been developed for transplant since the 1990s. Belatacept has the potential to improve and simplify the medication regimens of kidney transplant recipients and is also now being tested in experimental clinical trials for liver and pancreatic islet transplant.
Going for the constant—Emory researchers who study virus-like proteins (VLPs) also are focusing attention on components of the flu virus that remain relatively constant from one strain to another. They combined a standard strain of flu with VLPs containing the relatively constant viral protein M2. Used by itself, M2 offers little immune protection. The combination, however, provided a high level of protection to mice exposed to pandemic H1N1 and an H5N1 strain, suggesting that supplementation of seasonal flu vaccines may overcome limits of strain-specific vaccines.
Less pain, more antigens—A $10 million NIH grant will advance technology developed by Georgia Tech and Emory for painless self-administration of flu vaccine using patches with tiny microneedles that dissolve in the skin. The ability to painlessly immunize large numbers of people without need for medical personnel would increase the number of people being vaccinated, especially children and the elderly. Better yet, the microneedle patch appears to be more effective at vaccine delivery than traditional syringes because of the large number of antigen-presenting cells that reside in the skin.
Glioblastoma multiforme—This most common and primary brain tumor often recurs because cancer cells hide in surrounding brain tissue and survive initial treatment. Mouse studies in Emory’s brain tumor nanotechnology lab show that tiny, antibody-linked particles of iron oxide bind to and kill human glioblastoma cells without causing toxicity to normal brain cells. The particles also make tumor cells more visible on MRI. Clinical trials are on the horizon.
Solid tumors—Complete tumor removal is the most important predictor of patient survival. Biomedical engineers at Emory, Georgia Tech, and University of Pennsylvania have developed a handheld SpectroPen that allows surgeons to visualize tumor edges and spot cancer cells in lymph nodes during surgery. The pen detects light from tiny gold particles coupled to fluorescent dye and an antibody that sticks to tumor cells more than normal ones. Investigators hope to begin clinical trials in lung cancer soon, but the SpectroPen already is being used at the University of Georgia College of Veterinary Medicine to treat dogs with naturally occurring tumors.
Head and neck cancer—Emory and Georgia Tech researchers are coupling gold nanoparticles with antibodies against a growth factor common to this type of cancer. When the nanoparticles travel to cancers in the soft tissues of the mouth and throat, researchers use a laser to apply energy. The gold particles absorb this energy and convert it to heat, selectively killing cancer cells and sparing normal ones. Animal studies of toxicity and efficacy are required before clinical testing can be done in humans.
Apica Cardiovascular, a company started by Emory and Georgia Tech to develop a proprietary device that provides access to a beating heart during surgery, recently received $5 million in venture capital funding. The technology attaches a conduit to the beating heart so surgeons can deliver therapeutic devices, such as aortic or mitral valves, without loss of blood that occurs with conventional sutures, thus improving safety and decreasing procedure time and costs. Apica recently was named “start-up of the year” by Emory’s Office of Technology Transfer.
Researchers at Georgia Tech and Emory received a $14.6 million contract from NIH to translate relatively mature nanotechnologies into clinical applications for heart disease. Their goals are four-fold: (1) developing nanoparticle probes to image and characterize atherosclerotic plaques to detect early-stage disease and determine which plaques will grow and rupture; (2) determining presence or levels of protein markers, reactive oxygen species, or micro-RNAs as indicators of the presence and stage of atherosclerosis; (3) using nanoparticles to deliver therapeutic agents in a specific, sufficient, and sustained manner to localized vascular lesions; and (4) delivering patient-specific stem cells to vasculature and heart tissue damaged by atherosclerosis.
Collaboration between Emory and Children’s Healthcare of Atlanta grew this year with establishment of the Emory-Children’s Pediatric Research Center, linking investigators in cancer, transplant, cystic fibrosis, and other areas with pediatricians treating these diseases.
Another new collaboration, the Center for Pediatric Nanomedicine, includes physicians and scientists from Georgia Tech, Emory, and Children’s Healthcare, who are working to develop nanoscale structures to better diagnose and treat diseases and repair damaged tissues.
Emory medical faculty provide almost 4 million patient services a year, a substantial proportion of all care in Atlanta, from fetal medicine to geriatrics, from preventive and primary care to some of the most specialized care in the region. They provide this care in the six hospitals and various clinics of Emory Healthcare, the largest, most comprehensive health system in Georgia, and in Emory’s long-term affiliates: Grady Memorial Hospital, the Atlanta VA Medical Center, and Children’s Healthcare of Atlanta, with which Emory shares the largest pediatric multispecialty group practice in the state.
Last March, surgeons at Emory University Hospital performed a hand transplant on a young college student, placing Emory among only four centers to have successfully performed the procedure. Before joining Emory to direct the Emory University-Veterans Affairs Vascularized Composite Allograft Program, the only VA-approved limb transplant program in the country, surgeon Linda Cendales trained at University of Louisville, where she was on the team that performed the nation’s first and the world’s longest surviving hand transplant. The 19-hour surgery at Emory involved connection of numerous structures, including, bones, tendons, nerves, vessels, and skin.
Pediatric endocrinologist Eric Felner is leading a multi-site clinical trial to study effectiveness of alefacept, an immunosuppressant that attacks a subpopulation of renegade T cells, in controlling type 1 diabetes. This drug has gained FDA approval for treatment of psoriasis, and investigators hope they can use it to deactivate overactive T cells that attack insulin-producing cells in the pancreas.
Valve replacement—Catheter-delivered replacement heart valves should be the new standard of care for patients too frail or sick to withstand surgical valve replacement. That’s the conclusion of cardiologist Peter Block, principal investigator of a clinical trial that followed 358 Emory University Hospital patients with severe aortic stenosis. Patients who had replacement heart valves delivered by catheter were more likely to survive a year than patients who were treated without replacing their original valves. During the transcatheter aortic valve implantation, doctors feed the new valve, mounted on a wire mesh on a catheter, into a small incision in the groin or chest wall. When the valve is expanded, it pushes aside the diseased valve, allowing blood to flow normally.
Repair of aortic aneurysm—Conventional surgical repair of abdominal aortic aneurysm is not a viable option in about half of patients with this disorder because of the complexity of their disease. With the recent arrival of vascular surgeon Joseph Ricotta, Emory became the only institution in the Southeast offering high-risk patients fenestrated and branched endografts: stents with reinforced openings (fenestrations) or branches that allow the physician to attach arteries that lead to other organs. The endograft is delivered to the site of the aneurysm by catheter. The procedure is safe and effective for high-risk patients, and it requires no incision, reduces hospital stay, and speeds recovery.
Clinical trials—Emory’s Winship Cancer Institute has the most active clinical trials program in the state, including study of image-guided radiotherapy for painful metastasis of tumors to the spine, new techniques to improve detection of recurrent prostate cancer, and more powerful treatments for patients with recurrent, drug-resistant ovarian cancer. Winship also is leading a myeloma trial in which combination of an antibody engineered to attack a myeloma protein with standard drugs has produced a positive response in 83% of patients.
Personalizing treatment—Winship is one of 14 facilities in a National Cancer Institute-endorsed consortium formed to catalog genetic changes in lung cancer. The study’s goal, according to lung cancer specialist and principal investigator Fadlo Khuri, is to establish a fingerprint for each of the genetic changes or mutations found in as many as 50% of all lung cancers, which will aid clinicians in devising personalized, targeted therapies for individual patients.
Emory professor of medicine Ruth Parker is known for her work on health literacy. But what if reading isn’t enough? Parker co-led a yearlong study, published in JAMA, of 200 top-selling over-the-counter (OTC) oral liquid medications for children. Most contained variable and inconsistent dosing directions; nearly half had directions that did not match the measuring device included. Medications studied included 99% of U.S. analgesic, cough/cold, allergy, and gastrointestinal OTC oral liquid products with dosing information for children younger than 12. This patient safety issue needs urgent attention, says Parker.
Tim Buchman, founding director of Emory’s Center for Critical Care, is taking predictive health to the bedside in Emory’s critical care units. While most predictive health focuses on preventing and managing risks of chronic illnesses, Buchman wants to predict and head off immediate threats to life—an abnormal heart rhythm, a sudden increase or drop in blood pressure, or a seizure—before they happen. The body’s capacity for moment-to-moment adaptation in response to changing physiologic demand is the true signature of health, says Buchman. And loss of adaptive capacity—increasing regularity in the face of everyday changes in the immediate environment—signals risk for sudden deterioration.
That’s why Emory Hospital uses adaptive support ventilation for patients on ventilators, varying the size of breaths and intervals between breaths while minimizing the work of breathing, just as natural physiology expects. He and his colleagues also are studying waveforms of patients who go on to have a life-threatening event to see whether patterns of heart rate and blood pressure have predictive value for other patients. The goal, he says, is to peer a few minutes into the future, just far enough to prevent disaster and guide the patient back on course.