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Tag Archives: P4 Medicine Update 10/5/11
Researchers at Mount Sinai School of Medicine have identified a new drug target that may treat and/or prevent heart failure. The team evaluated failing human and pig hearts and discovered that SUMO1, a so-called “chaperone” protein that regulates the activity of key transporter genes, was decreased in failing hearts. When the researchers injected SUMO1 into these hearts via gene therapy, cardiac function was significantly improved. This research indicates that SUMO1 may play a critical role in the pathogenesis of heart failure. The data are published online in Nature.
Led by Roger J. Hajjar, MD, Director of Mount Sinai’s Wiener Family Cardiovascular Research Laboratories, and the Arthur and Janet C. Ross Professor of Medicine, Mount Sinai School of Medicine, the team has been evaluating the transporter gene SERCA2a in patients with severe heart failure as part of the CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial. When delivered via an adeno-associated virus vector—an inactive virus that acts as a medication transporter—into cardiac cells, SERCA2a demonstrated improvement or stabilization with minimal side effects. However, they found that while injection with SERCA2a restored cardiac function, over time the new SERCA2a became dysfunctional. This indicated that something else upstream from SERCA2a was causing the dysfunction in the heart.
Changwon Kho, PhD and Ah Young Lee, PhD, two postdoctorate students in the study of cardiac proteins at Mount Sinai School of Medicine, identified SUMO1 as the regulator of SERCA2a, showing that it enhanced its function and improved its stability and enzyme activity. Dr. Hajjar and his team studied human and animal models and found that when SUMO1 was decreased, SERCA2a became dysfunctional, showing that SUMO1 plays a protective role. When the team injected SUMO1 as a gene therapy, they found that it protected SERCA2a from the oxidative stresses and dysfunction that are prevalent in heart failure.
“Our experiments over the last four years beginning with the discovery of SUMO1 as an interacting protein of SERCA2a have shown that it plays a critical role in the development of heart failure,” said Dr. Hajjar. “In fact, SUMO1 may be a therapeutic target at the earliest signs of development, and may be beneficial in preventing its progression, a much-needed advance for the millions suffering from this disease.” Read more…
People who received intensive medical treatment following a first stroke had fewer second episodes and were less likely to die than people who received brain stents in addition to medical treatment, according to a new report in the New England Journal of Medicine, to be published online Sept. 7. All patients in the study had experienced one stroke and were considered at high risk for a second one.
Two co-authors on the paper were Methodist Neurological Institute investigators involved in the NIH-funded trial – Dr. David Chiu, principal investigator and medical director of Methodist’s Eddy Scurlock Stroke Center, and Dr. Richard Klucznik, co-investigator and interventional neuro-radiologist.
“This study is important because it will impact the way we treat stroke patients with arterial blockage in the brain,” said Chiu. “Over the past several years, we have improved treatments for intracranial atherosclerosis, and this research shows that intensive medical management is the key to preventing stroke recurrence.”
The Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study enrolled more than 450 patients at 50 sites across the United States
Co-authors say stroke patients with recent symptoms and intracranial arterial blockage of 70 percent or greater should be treated with an aggressive medical therapy that mirrors the regimen used in this trial. The regimen used in the study included daily blood-thinning medications and the aggressive control of blood pressure and cholesterol.
The Methodist Neurological Institute had the fourth largest patient enrollment nationwide (20). New enrollment in the study was stopped in April because early data showed significantly more strokes and deaths occurred among the stented patients at the 30-day mark compared to the group who received the medical management alone. All patients will continue to be followed for two years to determine the long term effects of both interventions.
In addition to the intensive medical program, half of the patients in the study received an intervention of a self-expanding stent called a Gateway-Wingspan that widens a major artery in the brain and facilitates blood flow. The study patients at Methodist who received a stent (10) suffered no complications from stenting. Read more…
GE Healthcare today announced plans to dedicate $1 billion in research and development spending over the next five years to expand its cancer diagnostic and molecular imaging capabilities, technologies for manufacturing biopharmaceuticals, and cancer research.
In line with those plans, its Clarient business is furthering development of a biomarker to identify patients who do not respond to taxane therapies for certain cancers. GE purchased Clarient last year for around $580 million with an eye toward combining Clarient’s biomarker efforts with its existing imaging capabilities.
“[W]ith a disease as complex and multifaceted as cancer, solutions need to be equally multifaceted and even more integrated, combining imaging, molecular diagnostics, and healthcare IT,” GE Healthcare President and CEO John Dineen said in a statement.
GE also announced a $100 million open innovation challenge “to find and fund ideas to accelerate detection of breast cancer and enable more personalized treatment.” The new investments, it said, will “focus on developing new oncology solutions and build on advanced technologies and research already in progress.”
One area of research focuses on a new biomarker, TLE3, which is being developed to help clinicians exclude patients least likely to benefit from taxane therapy. The biomarker is being developed by GE Clarient for breast cancer, lung cancer, and ovarian cancer.
In addition to improving patient outcomes, the work could save the healthcare system millions of dollars each year, GE said, adding it hopes to have a test based on the biomarker launched in 2013.
GE also plans to invest in molecular pathology for the development of cancer diagnostic technologies for “a clearer picture of pathways driving specific tumors,” as well as research that advances understanding of the molecular mechanisms of cancer.