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Cedars-Sinai

10 Big Ideas

10 Big Ideas

What ideas are shaping tomorrow’s medicine?

What are the coming innovations in treating heart disease and cancer?

What is the latest thinking in genetics and regenerative medicine?

From the minds of our scientists and clinicians, we bring you 10 noteworthy, thought-provoking ideas that have the potential to transform medicine.

01

Imagine you have been diagnosed with a heart problem. Your cardiologist must choose among 10 different medications. Some might help, but may also cause side effects. Fortunately, you have banked your own line of powerful stem cells. Developed from your own blood cells, stem cells can become any tissue, including lung, eye, muscle, or brain. Your cardiologist asks the laboratory to grow heart cells from your own stem cells. A few days later, your heart cells begin beating—in a petri dish. Now the 10 medications are applied to the cells. The process reveals which medication will work best for you, with a lowered risk of serious side effects.

“This is a technique that I think in less than 50 years will be routine,” predicts Clive Svendsen, PhD, a pioneer of stem cell science and director of the Cedars-Sinai Regenerative Medicine Institute (RMI). “Every patient at Cedars-Sinai could have their own pluripotent stem cell line banked in a repository.” It would be personalized medicine at its finest, and Dr. Svendsen sees Cedars-Sinai playing a pivotal role in developing the technology.

The key is the induced pluripotent stem (iPS) cell: a blank-slate human cell created by pushing ordinary adult cells “back in time” to an embryonic state. These extraordinary cells are expanding regenerative medicine, a rapidly developing field that seeks to understand how your own cells can be made to repair or regrow diseased or malfunctioning organs.

RMI scientists and their peers are already employing iPS technology to create powerful models that may radically change the way we understand Lou Gehrig’s disease, Alzheimer’s, corneal blindness, liver disease, and a host of other ailments. An explosion in discovery of new drug therapies isn’t far behind.

Dr. Svendsen is even using iPS technology to scrutinize that most elusive human condition: aging. “The fact that you can reprogram an 80-year-old cell and make it embryonic has to imply that aging in some sense is reversible,” he says. While there are no guarantees, this may eventually lead to a new understanding of the aging process in cells, why humans age, and how we may prevent it or at least slow it down. As aging is the major risk factor for most human diseases, this could have an enormous impact on medicine. “Pluripotent stem cell therapy is a quiet revolution that is going on in laboratories around the country and the world,” says Dr. Svendsen, “and to me it’s the most exciting area of science right now.” — Sarah Spivack LaRosa

02

Many adult conditions – such as obesity, diabetes, and atherosclerosis—have origins that can be traced as far back as fetal and neonatal development. A better understanding of neonatal nutrition could help optimize a baby’s growth and neurodevelopment in the first two years of life and potentially prevent adult diseases from taking root. The most logical place to start? Breast milk.

“There is a large gap in our knowledge of breast milk’s biochemical composition,” says Charles Simmons, Jr., MD, chairman of the Department of Pediatrics and director of the Division of Neonatology at Cedars-Sinai. “Doctors used to assume that all breast milks were created equal, but we’ve recently identified that there can be a difference of up to one-third in milk’s protein content from one mother to another.”

For “preemies”—who urgently need higher levels of calories and protein than full-term babies—any nutritional deficiency can have a dramatic impact on subsequent development and on health later in life.

Over the next five years, Dr. Simmons and his team at the Maxine Dunitz Children’s Health Center plan to analyze the breast milk of every new mother nursing a baby in the Neonatal Intensive Care Unit (NICU) in order to make effective nutritional adjustments. But there is a hurdle: Breast milk analysis is rarely performed in most medical centers, because laboratory assessment of breast milk is managed the same way as blood, i.e. involving a costly and lengthy process. Dr. Simmons and his colleagues are seeking more efficient analytic devices that will help doctors quickly determine how much nutritional supplementation premature babies need.

An additional component of the effort will be to pair the collected data with imaging strategies that can reveal the baby’s body fat composition and distribution. This dual approach will make it possible to provide premature babies with personalized nutrition and care. Dr. Simmons believes this could help prevent future generations from facing high rates of obesity, diabetes, or heart disease in adulthood. Says Dr. Simmons: “This is an elegant idea because it’s simple, potentially transformative, within reach—and yet still unattained.” —Louise Cobb

03

Now and then, a physician turns medical convention on its head. Such is the case of Armando Giuliano, MD. For years, the test to determine whether breast cancer had reached a woman’s lymph nodes involved radical removal of all the lymph nodes under the arm. Most of these nodes were devoid of cancer, and the patient often subsequently suffered from a swollen arm or shoulder dysfunction. Dr. Giuliano—executive vice chair of surgery for Surgical Oncology in the Department of Surgery at Cedars-Sinai—devised a technique for injecting a dye into the tumor and then visualizing the nodes where the dye appears. If these so-called sentinel nodes do not contain cancer cells, oncologists would know that the nodes further away from the breast were probably cancer-free, too, and would not need to be removed. This spares thousands of women from an operation that is not likely to offer any benefit.

If the sentinel nodes did contain cancer, the standard treatment was to remove not only those but also most or all of the lymph nodes in the patient’s armpit area. Dr. Giuliano and colleagues at the American College of Surgeons Oncology Group then showed that women who only had the involved sentinel nodes removed had the same survival rate—and were just as likely to be cancer-free five years later—as women who underwent additional surgery for the remaining nodes.

The results were radical enough to attract the attention of major cancer centers around the nation, which have already changed their practices based on the study. Others may be slower to follow suit. “For many doctors, this is a tough pill to swallow,” explains Dr. Giuliano, who serves in two capacities at the Samuel Oschin Comprehensive Cancer Institute, as associate director of Surgical Oncology and co-director of the Saul and Joyce Brandman Breast Center—a Project of Women’s Guild. “The belief that nodes have to be removed is so deeply ingrained.”

Still, he is hopeful that the new research will take hold in even more medical institutions across the country and beyond. “More and more surgeons are reducing the amount of radical lymph node surgery for breast cancer, and I’m just grateful to have been part of a transformative moment in my field.” —Jasmine Aimaq

04

Much of modern medicine is an unqualified success: We live longer, rarely die of infectious disease, and have wiped out some of history’s greatest villains such as polio and smallpox. Ironically, our success has left us with new challenges. “For all its miracles, modern medicine is largely failing to treat the new epidemics, such as chronic heart disease,” says C. Noel Bairey Merz, MD, a world-renowned cardiologist and director of the Women’s Heart Center at the Cedars-Sinai Heart Institute.

About 40 million Americans have tried alternative therapies such as chiropractic, acupuncture, or meditation. But not all such treatments are created equal, and medicine is hardly embracing crystal therapy and pyramid power. “What we’re looking for are complementary and alternative treatments we can study rigorously, and if there is high-quality scientific evidence of safety and effectiveness, we integrate them into mainstream care,” says Dr. Bairey Merz. That’s what the National Institutes of Health defines as “integrative medicine.”

Dr. Bairey Merz led a study showing that patients with heart disease who practiced transcendental meditation had lower blood pressure, blood sugar, and risk of sudden cardiac death than those who only followed medical protocols. “Those numbers simply can’t be ignored,” she says.

Alternative medicine may also be beneficial to people going through normal but sometimes debilitating processes such as menopause. Dr. Bairey Merz found that groups of women who received either real acupuncture or sham acupuncture (where toothpicks are tapped onto the skin to feel like needles) both reported fewer hot flashes. But when she analyzed blood samples from the two control groups, only the women who received real acupuncture showed a measurable decrease in stress hormones. For some patients, acupuncture might be a viable alternative to hormone therapy, which comes with risks and side effects.

Drug interactions and side effects are also a concern in another group of patients—the youngest and most vulnerable among us. Autism and attention deficit hyperactivity disorder (ADHD) are more prevalent than ever in children. While medication helps, Y. Jane Tavyev, MD, a pediatric neurologist at Cedars-Sinai’s Maxine Dunitz Children’s Health Center, hopes to find alternative treatments that work. “We’re actively researching how to treat these conditions differently,” says Dr. Tavyev, who is launching a study on yoga and autism.

“We have to think outside the box when looking at the cause and treatment of many diseases,” she adds. “In searching for the cause, we can assess environmental factors that may be interacting with a genetic predisposition. When deciding on a treatment, there may be good options other than medications.”

In the U.S., 42 prominent academic medical institutions, including Cedars-Sinai, Harvard, Yale, Duke, and the Mayo Clinic, are embracing integrative medicine modalities. Doctors are usually trained in “silos” of specialized knowledge, but, increasingly, they are learning to treat the whole person, look at every aspect of their patients’ lives, prevent disease, and become creative, well-rounded healers. And that’s a pretty radical idea. —Jasmine Aimaq

05

Of all the wondrous things our bodies can do, none is as romanticized as the beating of our hearts. On the medical front, matters of the heart are a different story. Heart disease and heart failure are among the major health challenges of our time. And when transplantation is the only option, the wait for a donor heart is often long and uncertain. Many patients with end-stage heart disease die while awaiting a donor organ. How do we bridge the time between needing and receiving a heart transplant for patients who would otherwise not survive? The Total Artificial Heart is the answer.

Our heart has two ventricles, and it is usually the left one that fails because it does most of the work. “We’ve long had devices that increase blood flow to one ventricle, staving off disaster while the patient waits for a donor organ,” says Jon Kobashigawa, MD, director of the Advanced Heart Disease and Heart Transplant programs at the Cedars-Sinai Heart Institute. “But in end-stage heart disease, both ventricles fail, and that’s a catastrophe.”

Enter the world’s first and only FDA-approved Total Artificial Heart, which temporarily replaces both ventricles, eliminating the source and symptoms of end-stage heart failure. It gives those patients who are in greatest need a mechanically functioning heart while they wait for a transplant. The device, manufactured by SynCardia, is implanted via open-heart surgery, just like a donor heart, and is available instantly at many institutions, including Cedars-Sinai, so there is no wait. “It’s a quantum leap in cardiac disease treatment,” says Dr. Kobashigawa.

The 13-member multidisciplinary team at the Cedars-Sinai Heart Institute was the first in Los Angeles to complete certification to implant the SynCardia Total Artificial Heart. More than 900 patients have received the Total Artificial Heart in certified centers in North America, Australia, and Europe. “It’s new technology, so it’s still viewed cautiously,” Dr. Kobashigawa says, “but with current success rates, more and more patients will benefit from this breakthrough invention.”

Patients stay in the hospital afterward because the artificial heart’s batteries are charged by a large machine to which it is tethered. That may soon change with development of a mobile battery pack to allow patients with a Total Artificial Heart to move around freely. Weighing around 13 pounds, it is worn like a backpack and provides a continual charge, so patients can return home and regain some normalcy while awaiting a transplant.

The Total Artificial Heart cannot replace a permanent organ because the batteries do not last long enough, although Dr. Kobashigawa believes that some day technology will change that. “Batteries will eventually become much smaller and last longer,” he explains, “and mechanical hearts may one day work just as well as donor hearts.” Until then, the Total Artificial Heart remains an extraordinary technical innovation and an almost miraculous temporary solution for patients with end-stage heart failure. —Jasmine Aimaq

06

Mapping the human genome is sometimes described as today’s equivalent of the moon landing—a scientific achievement so breathtaking that few would have thought it possible when it was first proposed. Exploring our species’ entire hereditary information, the project has radically deepened our understanding of DNA and our ability to treat many diseases based on a person’s specific genetic makeup. So, if we can treat some genetic cancers with a simple drug, why can’t we do the same for genetic disorders such as dwarfism?

David L. Rimoin, MD, PhD, director of the Medical Genetics Research Institute at Cedars-Sinai, thinks we can. Dr. Rimoin and his colleague William R. Wilcox, MD, PhD, are helping develop the first viable treatment for achondroplasia, the most common cause of dwarfism. In achondroplasia, which accounts for around 70 percent of dwarfism cases, the trunk is normal but the arms and legs are very short and the head is disproportionally large. The condition is caused by a genetic mutation that leads to abnormal bone growth.

“The effects of achondroplasia can be serious and painful,” says Dr. Wilcox, director of the Cedars-Sinai Skeletal Dysplasia Morphology and Molecular Laboratory, who explains that fluid buildup in the brain, sleep apnea, neurological changes, and spinal stenosis are common symptoms. “Life can be very challenging for little people,” he adds.

Doctors can treat many of the complications associated with achondroplasia, but the only way to bring the body into better proportion is a controversial and complex series of limb lengthening surgeries that can take years and result in various complications. “For ethical and medical reasons, these operations are rarely performed anymore here at Cedars-Sinai,” says Dr. Rimoin, who received the American College of Medical Genetics Foundation’s Lifetime Achievement Award in 2010. “It is time we offer a viable option.”

With that goal in mind, Drs. Rimoin and Wilcox and their team, in collaboration with BioMarin Pharmaceutical, Inc., are exploring a novel solution: a drug that involves a peptide—a type of molecule that exists naturally in the human body. “We’ve discovered that by modifying a peptide that regulates bone growth, we can actually counteract the effects of the gene mutation that causes dwarfism,” Dr. Rimoin explains. The revolutionary treatment, which enters Phase 1 clinical trials in 2012, consists of injections that could change the course of an infant’s bone development— and, in the process, of that child’s entire future. —Jasmine Aimaq

07

Here is a non-controversial statement: Nobody likes a tumor, whether is it behaving badly or benignly. If we are harboring one, we usually want it taken out, and the sooner the better. What is controversial, and indeed revolutionary, is the idea that we could let some tumors simply be.

Such is the basis of research spearheaded by Edwin M. Posadas, MD, clinical director of the Genitourinary Medical Oncology Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. “We may be on the verge of a treatment that stops cancer from spreading to other organs, making an existing tumor much less dangerous, to the point that removing it would not be required,” says Dr. Posadas, whose focus is on late-stage prostate cancer.

Dr. Posadas began by studying mechanisms through which malignant cells spread from the prostate to other parts of the body, a process called metastasis—a hallmark of late-stage cancer. His team identified a protein that regulates that mechanism, and Dr. Posadas hopes the discovery will lead to a drug that prevents metastasis, sparing prostate cancer patients the risks and hardship of surgery, radiation, or chemotherapy.

“What many people don’t realize is that the original tumor itself isn’t what usually kills you, even when it’s malignant,” Dr. Posadas explains. “It’s when that cancer starts to metastasize or spread that death becomes a serious possibility.” And while his investigation is currently limited to late-stage prostate cancer, he hopes it will lead to similar research and treatments for early-stage patients and for those suffering from other types of cancers. “If we can discover a true anti-metastasis therapy,” says Dr. Posadas, “we will have altered the entire landscape of cancer treatment. It would be nothing less than a paradigm shift.” —Jasmine Aimaq

08

Throwing stones at castle walls is one way to attach an enemy, but sneaking inside makes the target much more vulnerable. Researchers at Cedars-Sinai have employed a similar strategy to target important mechanisms inside breast and brain cancer cells.

Unlike other drugs that target cancer cells from the outside and often injure normal cells as a side effect, this therapy consists of multiple drugs chemically bonded to a “transport vehicle.” This tiny Trojan horse is called a nanoconjugate: the latest evolution of molecular drugs based on nanotechnology principles and designed to enter cells and alter defined targets within them.

Nanoconjugates are emerging as promising drug-delivery vehicles because their structure enables them to target discrete tumor cells, pass through biological barriers, and simultaneously carry multiple drugs. With inventive drug . engineering, the antitumor components attack molecules inside the cells that enable cancer to grow and spread.

Studies in animal models show this highly targeted, stealth approach using combinations of drugs to be more effective than standard cancer treatment methods.

“Our nanoconjugate appears to be a safe and efficient delivery method that may be tailored to treat a wide array of disorders,” says Julia Y. Ljubimova, MD, PhD, director of the new Nanomedicine Research Center in the Cedars-Sinai Department of Neurosurgery. “It’s nontoxic to normal tissue and, unlike other nanomedicine drugs, it doesn’t appear to cause dangerous allergic reactions.” Cedars-Sinai’s Nanomedicine Research Center was awarded a special series of five-year grants from the National Institutes of Health for speeding up novel methods of cancer treatment. —Louise Cobb

09

Soldiers injured in battle are usually stabilized in combat operating rooms, then flown on ICU-equipped planes to regional military medical centers. The coordination and communication needed to safely complete this two-step function is daunting. Therefore, the Department of Defense has engaged Cedars-Sinai to help redesign care protocols and operating room environments with a clear mandate: save military lives and reduce the immense stress on surgeons and their team in war zones. The big idea? This project could actually lead to the enhanced design of operating rooms in non-military hospitals, too.

“It turns out that much of what we’re doing on this project also makes sense in the regular operating room,” says Bruce L. Gewertz, MD, surgeon-in-chief at Cedars- Sinai. “By improving what’s already there and staying one step ahead of technology, we are now designing the operating room of the future.” That means rethinking everything, from basic things like lighting and ergonomics to how to integrate the most advanced new equipment.

Within a year, Cedars-Sinai will have completed a simulation room where the new ideas will be put into effect and tested—like intelligent software that can support surgeons who must make critical decisions in a matter of seconds, and information technology that ensures computers share information with each other as quickly as possible, so everyone in the operating room knows exactly what is transpiring in real time.

Dr. Gewertz, who is chair of the Department of Surgery, vice president for Interventional Services, and vice dean of Academic Affairs at Cedars-Sinai, also holds the H & S Nichols Endowed Chair in Surgery. He hopes that open plug-and-play will become the norm in the operating room of the future—the seamless integration of medical devices and having them recognize each other and work together instantly, even if they are manufactured by different companies. “That way we’ll always be able to acquire the very best equipment for our patients, without worrying about compatibility.”

Even with state-of-the-art technology, the human element will remain the most important component in the operating room. “Teamwork is always the most essential thing,” Dr. Gewertz says. “There is no technological solution without a human solution.” —Jasmine Aimaq

10

Part of being a great leader is having the courage to continually ask: Am I as good as I can be? To do this, you must have both the capacity and the will to improve. Over the years, that philosophy has been a key aspect of Cedars-Sinai’s success, and it is at the heart of a new initiative that will examine every step of the hospital’s clinical processes to ensure it is always providing the right care, in the right setting, with the right resources.

“It sounds simple, but it’s a goal that has eluded hospitals nationwide for decades,” says Glenn D. Braunstein, MD, who serves as Cedars-Sinai’s vice president for Clinical Innovation. “In our ongoing quest to set the highest standards of care and to make significant contributions to the practice of medicine, we’re holding up a mirror and looking directly into it. We’ve discovered a few imperfections, and so are developing new approaches that will likely raise the bar for hospitals nationwide.”

The initiative is exploring many aspects of healthcare, including ways to take action before health problems become more difficult and expensive to solve, methods to improve coordination of care and ensure seamless transitions between levels of care, and mechanisms to avoid unnecessary hospital admissions.

“In the past, for example, we might have admitted a patient and run tests over four or five days,” says Dr. Braunstein. “We recently redesigned our process so that, now, patients can be admitted to an observation room for 24 hours, where physicians observe their symptoms and reactions, and run tests as necessary.” The process is less stressful for the patient, allows physicians to make more prudent and deliberate choices, and is more cost-effective.

As part of Cedars-Sinai’s Best Practices program, the Medical Center is also using a clear and careful system to ensure each patient receives the most appropriate treatment for his or her specific situation. “We first identify the medical issue, then do an evidence-based review of research in the medical literature,” Dr. Braunstein explains. “Then we look at how other medical organizations are treating the problem, examine internal data and benchmark data, and develop multidisciplinary teams—doctors, nurses, social workers, pharmacists, emergency room staff, and other healthcare team members—tailored to each individual patient’s exact needs.”

The Best Practices model includes software that provides physicians with information about possible tests or treatments to consider through a series of pop-up windows that can confirm the doctor’s inclination or make other suggestions at the time orders are being entered. Other software compares a physician’s clinical practice patterns and patient outcomes with local and national data on how other physicians treat patients with similar medical conditions.

In the final analysis, are we as good as we think we are? “The answer must always be ‘no,’” Dr. Braunstein explains, “because anything else could make us complacent.” —Jasmine Aimaq

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