Lupus: New Hope for a Complicated Illness

FOR PEOPLE WITH LUPUS, EACH DAY CAN BEGIN WITH THE challenge of getting out of bed. Simple, everyday
tasks — putting on a kettle for tea, buttoning a shirt — can become daily feats of perseverance, since lupus is a disease in which the immune system attacks the body’s own cells and tissues, resulting in crushing fatigue, painful joint swelling, and persistent skin rashes. For hundreds of thousands of people — mostly women — this is their daily reality. Until recently, they had little expectation that it would improve.
     Recruitment of a respected lupus clinical researcher to P&S offers new hope. The rheumatology division in the Department of Medicine will offer clinical trials, basic research, and the latest in patient care through a new lupus clinic, directed by Betty Diamond, M.D., the Dorothy and Daniel Silberberg Professor of Medicine and Professor of Microbiology. Dr. Diamond, one of the nation’s most highly respected and innovative scientific investigators, has directed much of her basic and clinical research to the study of lupus. P&S recruited Dr. Diamond in 2004 from Albert Einstein College of Medicine, where her team was credited with elucidating a potential mechanism for cognitive decline in lupus and identifying new therapeutic possibilities.
     The clinic will focus specifically on providing lupus patients with the best care and state-of-the-art treatment, while maintaining an ambitious research program designed to close the gap between basic research and clinical applications. The rheumatology division has a strong foundation in clinical and basic science research. It is one of only nine NIH-designated “Autoimmune Centers of Excellence,” a consortium of research centers across the country geared toward fighting autoimmune diseases like lupus. The rheumatology division is also a member of the Lupus Clinical Trials Consortium, a philanthropically funded network of 23 medical centers involved in clinical trials in lupus, and is conducting studies in lupus supported by the Immune Tolerance Network.
     “One of the things that make this clinic unique is the communication between basic science and the clinical researchers,” says Cynthia Aranow, M.D., assistant professor of medicine and co-clinical director of the clinic with Meggan Mackay, M.D., assistant professor of medicine. “It’s a true working example of translational research.”
     Lupus has stymied medical researchers for years. Not only are its symptoms frustratingly vague and difficult to diagnose, but its environmental and genetic triggers are poorly understood. Treatment has largely been limited to alleviating symptoms: anti-inflammatories, steroids, and antimalarial drugs for mild symptoms such as joint swelling, and, when all else fails, immunosuppressant drugs to stop the immune system’s attacks on organs.
     Today is an exceptionally exciting time for potential treatments: Years of basic research and translational studies have suddenly caught up with one another, producing an array of new treatments that are ready for testing. “The major challenge [for researchers] is trying to figure out how to dampen the immune system without impairing its ability to fight infections,” Dr. Aranow says. “The clinic will investigate several such interventions.”
     The clinic will oversee both clinical trials and state-of-the-art care to patients seeking the expertise of the clinic and patients from the surrounding, predominantly Dominican neighborhood. “We know that lupus seems to affect Hispanics and African-Americans with a higher prevalence and severity,” says Dr. Aranow. “The clinic will reach out to serve our community.”
     Drs. Aranow and Mackay expect the clinic to provide ongoing care for about 250 to 350 patients, in addition to those participating in clinical research and clinical trials. More information is available from the clinic, 212-342-3713.


With Botanical Medicine Course, P&S Returns to its Roots
With Botanical Medicine Course. P&S Returns to its Roots
WHEN COLUMBIA’S ROSENTHAL CENTER FOR COMPLEMENTARY and Alternative Medicine launched its CME course in botanical medicine in 1996, it was to considerable controversy. “The first time we offered this course, a P&S alumnus threatened to picket us,” says Fredi Kronenberg, Ph.D., professor of clinical physiology in rehabilitation medicine and director of the center.
     A decade later, the same course, “Botanical Medicine in Modern Clinical Practice,” draws 250 physicians and medical professionals from around the country each year and the center has to turn participants away to maintain the intimate and interactive course format. “We have provided training for more than 2,000 physicians, nurses, and other clinicians over the years,” says Dr. Kronenberg.
     It has been a long road. When Dr. Kronenberg started the Rosenthal Center at Columbia in 1993, botanical medicine was still largely underground in the medical community. But she and her colleagues soon discovered that underground did not mean nonexistent. To understand the needs of researchers and clinicians, Dr. Kronenberg distributed a questionnaire to the medical center faculty.
     “We were surprised to get back nearly 400 responses from virtually every department,” she says. Predictably, one-third of the responders said that the center was wasting time and money, but another third were curious enough to ask for more information. Perhaps most surprising, however, was the number of respondents who confessed their quiet, late night, back-of-the-lab experiments, patient referrals, or even treatment of patients with botanicals, acupuncture, homeopathy, Alexander technique, and Chinese medicine.
     “It was all very furtive, but a lot was going on under the radar screen,” Dr. Kronenberg says.
The questionnaire results emboldened Dr. Kronenberg to bring the research above ground; the Rosenthal Center became a place where faculty members could carry out legitimate research projects on complementary and alternative treatments in the light of day and in collaboration with colleagues — and even to challenge and critically question one another in large or small lecture forums. “When the center began it became legitimate for researchers and clinicians to talk about things they had already been doing for a long time,” says Dr. Kronenberg.
     The course in botanical medicine is a way to share scientific knowledge about herbs with the larger medical community. It also serves the practical function of closing the gap between patients who have increasingly been using botanical remedies for years and physicians who know little about the herbs or what interactions they might have with Western medications. “We’re exposing people to information. Even if they never want to use it themselves, they at least are more conversant and can help guide their patients with greater knowledge,” says Dr. Kronenberg.
     The Rosenthal Center began offering another CME course in integrated pain medicine five years ago. A course in nutrition, in collaboration with the University of Arizona, offered for the past two years in Tucson, will be held in New York City in 2006 (April 30-May 3) and will include a full-day public forum. As the medical community becomes more accepting, Dr. Kronenberg sees the expansion continuing. “We have an ongoing NIH-funded clinical trial of an herbal alternative to HRT for menopausal women; basic science research on anti-cancer properties of herbs; an ethnobotanical study of herbs used by ethnic communities in New York, and we are beginning a study of Chinese medicine, including acupuncture, for dysmenorrhea in women,” she says.
     Dr. Kronenberg’s next goal, and her next fund-raising challenge, is to build a botanical research center that would run the gamut from basic science research to clinical research. Such a center would provide a broad range of services such as finding sources for appropriate herbal products for research and developing successful NIH grant applications, as well as a phytochemistry core laboratory for quality control and stability testing and other phytochemistry needs for all at Columbia doing botanical research.
     “We already have a great team of phytochemists, physiologists, molecular biologists, botanists, ethnobotanists, epidemiologists, and herbalists and a strong partnership exists between Columbia’s Department of Chemistry and the New York Botanical Garden’s ethnobotanists, plant geneticists, and botanists,” Dr. Kronenberg says.Andrew Weil     
Andrew Weil, derector of integrative medicine at the University of Arizona
medical school anda faculty member at the annual botanical medicine
course

     With the renewed interest in teaching about botanical medicine and collaboration with the New York Botanical Garden, P&S is, in a sense, returning to it roots, literally and figuratively. In the early 1800s, Dr. David Hosack taught about medicinal plants as professor of materia medica at P&S. His medical training included study under eminent botanists as well as physicians. Dr. Hosack started the Elgin Botanic Garden and herbarium in 1801 on a parcel of land that is now Rockefeller Center to provide medical students with a place to study living medicinal plants. Columbia subsequently contributed many of Dr. Hosack’s botanical specimens to the New York Botanical Garden, founded in 1891 by Columbia botany professor Nathaniel Lord Britton.
"On the day at the New York Botanical Garden, course participants learn about the botanical sources of many modern drugs, including atropine, digoxin, ephedrine, quinine, pilocarpine, and reserpine, among many others,” Dr. Kronenberg says. “They see the live plants and learn about some of the ethnomedical traditions for which herbal remedies are paramount, such as those practiced in urban areas around the country and particularly in New York City.”


How Stem Cells Can Repair Damaged Hearts

THE STATISTICS ARE STAGGERING: HEART DISEASE IS THE country’s No. 1 killer. Seventy million Americans have some form of cardiovascular disease. Nearly a million people die of heart disease each year.
     Warren Sherman, M.D., director of cardiac cell-based endovascular therapies at Columbia’s world-renownedHow Steam Cell Can Repair Damaged Hearts cardiology group — CIVT, or the Center for Interventional Vascular Therapy — has spent his career fighting back against these numbers. From his earliest days as an interventional cardiologist, Dr. Sherman pioneered noninvasive, catheter-based techniques to clear blocked arteries, insert stents, and repair damaged hearts.
     Now, Dr. Sherman is investigating the use of stem cell-based therapies to repair the devastating damage of a heart attack. When a heart attack occurs, a section of the heart muscle is deprived of essential oxygen and nutrients, leading to tissue death. The affected part of the heart is rendered profoundly weak. While modern treatment is able to limit consequences of the damage, all too often the process leads to congestive heart failure.
     Conventional wisdom holds that the heart, unlike self-regenerative organs like the skin and liver, lacks the capacity to repair damaged tissue. “Most forms of damage that affect the heart are permanent,” says Dr. Sherman. “When a person has a heart attack the traditional thinking is that there is no potential for the heart to regenerate. Instead, the story goes, the best it can do is generate scar tissue.”
     But Dr. Sherman and other researchers have begun to poke holes in that conventional wisdom, identifying cells that may be able to replace damaged heart tissue with new growth. Dr. Sherman has found that certain skeletal muscle cells, skeletal myoblasts, can be applied to damaged areas and repair the tissue. “It’s been established that these cells can be harvested, isolated, grown in culture, and then implanted in the heart, where they can replace some of the muscle tissue that has died,” he says.
     The first surgical implantation of skeletal myoblasts in a human took place in 2000. In 2001, Dr. Sherman participated in another first: using a specially designed catheter to deliver the cells with pinpoint accuracy to the precise site of the damage in human patients who had a history of acute myocardial infarction and congestive heart failure.
     By developing a method to implant cells in the heart using a catheter, invasive surgery could be avoided. To date, in published and unpublished studies, Dr. Sherman estimates that nearly 200 patients have undergone skeletal myoblast implantation, by either surgical or catheter procedures, in an attempt to repair damaged heart tissue.
     Much of this research has yet to be systematically analyzed, but anecdotal evidence shows that many patients who have undergone the stem cell therapy have improved heart function and generally feel better after the procedure.
     There is still much work to be done and Dr. Sherman plans to continue to pursue the promise of stem cell therapy for heart patients at CIVT. Studies are ongoing at Columbia using bone marrow-derived cells in patients with acute heart attacks; others will soon follow in patients with advanced coronary disease and heart failure. In Spring 2006, Dr. Sherman expects to begin a Phase II randomized, controlled multicenter study at Columbia on the therapeutic use of skeletal myoblasts. Much of this work has occurred in collaboration with other Columbia researchers, including Drs. Silviu Itescu, Eric Rose, Martin Leon, Tim Martens, and others.

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