Research on immune cells “exhausted” by chronic viral infection provides clues on how to refine cancer immunotherapy. The results were published Tuesday, Dec. 3 in Immunity.
Scientists at Emory Vaccine Center, led by Rafi Ahmed, PhD, have learned about exhausted CD8 T cells, based on studying mice with chronic viral infections. In the presence of persistent virus or cancer, CD8 T cells lose much of their ability to fight disease, and display inhibitory checkpoint proteins Read more
Emory neurosurgeon Robert Gross was recently quoted in a Tennessee newspaper article about a clinical trial of cell therapy for stroke. He used cautionary language to set expectations.
“We’re still in the very early exploratory phases of this type of work,” Gross told the Chattanooga Times Free Press. “In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that.”
A more preliminary study (just 18 patients) using the same approach at Stanford and University of Pittsburgh was published this summer in Stroke, which says it was the “first reported intracerebral stem cell transplant study for stroke in North America.” The San Diego Union Tribune made an effort to be balanced in how the results were described:
Stroke patients who received genetically modified stem cells significantly recovered their mobility… Outcomes varied, but more than a third experienced significant benefit.
The newspaper articles made us curious about what these cells actually are. They’re mesenchymal stromal cells, engineered with an extra modified Notch gene. That extra gene drives them to make more supportive factors for neurons, but it doesn’t turn them into neurons. Read more
But then I realized that this might beÂ an example of “burying the lead,” since we haven’t made a big hoopla about the underlying vaccineÂ studies, conducted by Rama Amara. Some of these studiesÂ showed that a majority of monkeys can beÂ protected from repeated viral challenge.Â TheÂ more effective vaccine regimens include adjuvants such asÂ the immune-stimulating molecules GM-CSF or CD40LÂ (links are the papers on the protective effects). Read more
Biomarkers circulating in the bloodstream may serve as a predictive window for recurrent stroke risk and also help doctors accurately assess what is happening in the brains of patients with acute traumatic brain injury (TBI).
Michael Frankel, MD
Researchers at Emory University School of Medicine, led by principal investigator Michael Frankel, MD, Emory professor of neurology and director of Grady Memorial Hospitalâ€™s Marcus Stroke & Neuroscience Center, are studying biomarkers as part of two ancillary studies of blood samples using two grants from the National Institutes of Health.
In the $1.47 million, four-year grant called â€œBiomarkers of Ischemic Outcomes in Intracranial Stenosisâ€ (BIOSIS), Emory researchers are analyzing blood samples from 451 patients from around the country who were enrolled in a study known as SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis), the first randomized, multicenter clinical trial designed to test whether stenting intracranial arteries would prevent recurrent stroke.
Researchers in the SAMMPRIS study recently published their results in the New England Journal of Medicine, showing that medical management was more effective than stenting in preventing recurrent strokes in these patients. Frankel’s BIOSIS research team is using blood samples from these same patients to continue learning more about the molecular biology of stroke to predict risk of a stroke occurring in the future.
â€œOur goal is to learn more about stroke by studying proteins and cells in the blood that reflect the severity of disease in arteries that leads to stroke. If we can test blood samples for proteins and cells that put patients at high risk for stroke, we can better tailor treatment for those patients,â€ says Frankel.
Patients with narrowed brain arteries, known as intracranial stenosis, have a particularly high risk of disease leading to stroke. At least one in four of the 795,000 Americans who have a stroke each year will have another stroke within their lifetime. Within five years ofÂ a firstÂ stroke,Â the risk for another stroke can increase more than 40 percent. Recurrent strokes often have a higher rate of death and disability because parts of the brain already injured by the original stroke may not be as resilient.
The other study, â€œBiomarkers of Injury and Outcome in ProTECT IIIâ€ (BIO-ProTECT)” is a $2.6 million, five-year NIH grant in which Frankelâ€™s team will use blood to determine what is happening in the brain of patients with acute TBI.Â The blood samples are from patients enrolled in the multicenter clinical trial ProTECT III (Progesterone for Traumatic brain injury, Experimental Clinical Treatment), led by Emory Emergency Medicine Professor, David Wright, MD, to assesses the use of progesterone to treat TBI in 1,140 patients at 17 centers nationwide.
In the BIO-ProTECT study, Emory is collaborating with the Medical University of South Carolina, the University of Pittsburgh, the University of Michigan and Banyan Biomarkers.
TBI is the leading cause of death and disability among young adults in the US and worldwide. According to the Centers for Disease Control and Prevention, approximately 1.4 million Americans sustain a traumatic brain injury each year, leading to 275,000 hospitalizations, 80,000 disabilities, and 52,000 deaths.
Acute TBI leads to a cascade of cellular events set in motion by the initial injury that ultimately lead to cerebral edema (swelling of the brain), cellular disruption and sometimes death. Tissue breakdown leads to the release of proteins into the bloodstream. These proteins may serve as useful biomarkers of the severity of the injury and perhaps provide useful information about response to treatment.
Using the large patient group in the ProTECT III trial, the researchers hope to validate promising TBI biomarkers as predictors of clinical outcome and also evaluate the relationship between progesterone treatment, biomarker levels and outcome.
â€œIf we can better determine the amount of brain injury with blood samples, we can use blood to help doctors better assess prognosis for recovery, and, hopefully whether a patient will respond to treatment with progesterone,â€ says Frankel.
The scientific part of the AIDS Vaccine 2010 meeting began Tuesday evening with an exciting summary of issues facing the field from NIAID director Tony Fauci. But before that, participants in this yearâ€™s conference got a chance to warm up with several â€œsatellite sessions.â€
One of them, â€œEffective Community Engagement in HIV Vaccine Research Among Communities and Researchers,â€ was organized by Paula Frew, PhD, director of health communications and applied community research at Emoryâ€™s Hope Clinic.
Two prominent themes emerged from this session. The first was that community members should be involved in clinical trials at every step of the process: from design and recruitment to dissemination of results.
â€œIn the past, scientists often came to the community late in the process, after a protocol for a study was already approved, and said: â€œWill you support what weâ€™ve already decided?â€ said Steve Wakefield of HIV Vaccine Trials Network. â€œThis doesnâ€™t work.â€
The Joint United Nations Programme on HIV/AIDS and AVAC presented proposed guidelines for â€œgood participatory practice,â€ analogous to good clinical practices.
Emory heart patient, Glenrose Gay of Vidalia was the first person in GA to receive a new aortic valve via catheter. Pictured here in 2007 with Emory cardiologists, Drs. Peter Block (left) and Vasilis Babaliaros.
Since October 2007, Emory University Hospital has been one of approximately 20 hospitals nationwide, and the only site in Georgia, studying a new non-surgical treatment option for patients with failing aortic valves. The life threatening heart condition,aortic stenosis, affects tens of thousands of Americans each year when the aortic valve tightens or narrows, preventing blood from flowing through normally.
As part of the Phase II clinical trial, researchers have been performing transcatheter aortic valve implantation (TAVI) comparing this procedure with traditional, open-heart surgery or medical therapy in high-risk patients with aortic stenosis.
During the TAVI procedure, doctors create a small incision in the groin or chest wall and then feed the new valve, mounted on a wire mesh on a catheter, and place it where the new valve is needed. This offers a non-invasive way for doctors to treat patients who are too ill or frail to endure the traditional open-heart surgical approach.
The study, published Wednesday in The New England Journal of Medicine (NEJM) followed 358 patients who received either catheter-delivered valves or standard non-surgical treatment.
The findings showed that 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. According to the authors, catheter-delivered valves “should be the new standard of care” for patients who are not able to undergo surgery.
“These results show great promise for patients with severe aortic stenosis and help us make a giant step forward in our battle against this common disease,” says Peter Block, MD, professor of medicine, Emory School of Medicine and principal investigator of the study at Emory. “They are especially important since the number of people with failing valves is expected to greatly increase as baby boomers continue to age.â€
Aortic valve stenosis often occurs with age, most commonly among elderly patients over 70 years of age, but can surface earlier in life in those with rheumatic heart disease or congenital abnormalities of the valve.
Approximately 90 patients have received new valves at Emory since the clinical trial started in 2007. Researchers hope to receive FDA approval in late 2011.
Having a newborn and managing all that comes with caring for that new little one is a big job. Add to that frequent trips to the ophthalmologist following a cataract surgeryâ€”yes, cataract surgery on a babyâ€”and you might have highly stressed parents. But the parents of little James and slightly older M.J. seem unfazed by all the medical appointments and additional duties that go along with caring for their young sons.
M.J. Burkett and James Weeks became patients in the IATS trial, which has treated 114 babies across the United States.
Both the boys, like 300 babies each year in the United States, were born with a cataract in one eye. In an infant, if the affected eye isnâ€™t surgically addressed within the first few months of life, that eye will not develop properly and vision can be permanently lost. These boys and their parents and 112 other young patients and their families have participated in the Infant Aphakia Treatment Study (IATS), a nationwide, multi-center clinical trial based at the Emory Eye Center. The 10-year study will evaluate whether replacing that lost lens with a contact lens or an intraocular lens (IOL) is preferable.
Adults typically get an IOL implant following cataract surgery. In the past, standard treatment was a contact lens for these babies. IATS randomized children into two groups: those who received IOL implants and those who received contact lenses. Those with IOLs also received glasses for residual vision correction. And both groups had daily patching of the unaffected eye to make sure that the newly corrected eye could become strong.
A team of professionals from Emory and beyond came together to provide the many layers of data necessary for the study. They included experts from the Rollins School of Public Health and the Department of Epidemiology and Data Coordinating Center in the Department of Biostatistics and Bioinformatics, as well as a visual acuity tester from the University of Alabama, Birmingham, who traveled to all sites to check these children.
Emory oncologist Ruth O’Regan, MD, is leading a trial testing whether Afinitor can reverse resistance to Herceptin in metastatic HER2-positive breast cancer patients. As part of the trial, some patients been receiving a drug called Afinitor (everolimus) along with chemotherapy and Herceptin (trastuzumab).
Ruth O'Regan, MD
About 25 percent to 30 percent of breast cancers are HER2 -positive, which means they test positive for a protein called human epidermal growth factor receptor-2 (HER2). This protein promotes the growth of cancer cells, making HER2 -positive breast cancers more aggressive than other types.
They also tend to be less responsive to hormone treatment. That’s the bad news. The good news is that this type of cancer responds extremely well to Herceptin.
Herceptin specifically targets HER2 cells, killing them while sparing healthy cells, so side effects are minimal. Its effectiveness has made Herceptin the gold standard of treatment for HER2 -positive breast cancer.
Although African Americans make up a significant share of HIV cases in the U.S., they are underrepresented in HIV clinical trials. New research shows that promotion of HIV clinical trials and participation by African Americans can be increased by coalitions that link community organizations to clinical-research institutions.
â€œCommunity organizations already have built trusting relationships in their communities,â€ saysÂ Paula Frew, PhD, assistant professor of medicine at Emory School of Medicine. â€œIf HIV/AIDS prevention and HIV clinical research become part of the agendas of these organizations, they can become ideal allies for increasing participation by community members who are at risk for disease.â€
If youâ€™d like to consider joining a clinical trial, a new secure website will make it easier. ResearchMatch.org will match any interested person living in the U.S. with researchers who are approved to recruit potential study volunteers.
Emory is one of 51 institutions participating in this first national, secure, volunteer recruitment registry. After registering at the website, potential volunteers can check out available trials. If a person indicates interest in a study, they are notified electronically about a possible match. Then they can decide whether to provide their contact information to a researcher.
ResearchMatch.org is a wonderful opportunity for those interested in participating in clinical research, says Arlene Chapman, MD, Emory professor of medicine and director of the ACTSI Clinical Interaction Network Program. Itâ€™s available to young and old, healthy or ill. And people with a rare disease can find out more about available research studies throughout the country.
The registry strictly protects anonymity. It also increases the chance to participate in local studies and saves much of the time typically spent finding out about eligibility for a particular study.
Service members returning from war historically have been haunted by traumatic memories related to combat. Problems can arise when these troublesome memories are suppressed instead of being confronted.
The military trains its service members well for combat, but teaching each individual how to deal emotionally with the trauma that comes with it is a challenge that has yet to be resolved. Unfortunately, many of those brave men and women have trouble admitting or recognizing an emotional problem. They tend to believe that avoiding troublesome memories is the best solution and do not come forward for help.
Once a service member returns home from a war zone, symptoms caused by haunting memories can arise and begin to interfere with every day activities. When those symptoms last for more than four weeks, it is likely that individual has posttraumatic stress disorder (PTSD).
Emory researcher Barbara Rothbaum, PhD, professor of psychiatry and behavioral sciences, Emory School of Medicine, and director of the Trauma and Anxiety Recovery Program, has been treating military personnel with posttraumatic stress for more than a decade, helping them to learn how to deal with the troubling memories. Through exposure therapy, the service members are taught that by re-living the traumatic event, they can begin to handle those memories when they surface.
Rothbaum is also a pioneer in exposure therapy using virtual reality software that was developed for both Vietnam veterans and service members returning from the war in Iraq.
Military commanders recognize that symptoms of PTSD are not as obvious as a physical injury, but nonetheless just as important, and they are ready to develop programs to quickly identify and treat active duty service members and veterans who are showing symptoms of PTSD before they worsen, says Rothbaum.
PTSD is treatable and treatments vary from exposure therapy to medication to meditation techniques. Symptoms include reliving the event; avoiding situations that stir up memories of the event; discomfort expressing feelings; being constantly on the lookout for danger; irritability; drinking or drug problems and employment, social and relationship problems.