Focus Area: Scleroderma Program
A nationally recognized leader in scleroderma and at the forefront of bedside-to-bench-to-bedside translational research, the Northwestern Scleroderma Program recently celebrated a significant milestone: the enrollment of its 600th patient since the program’s establishment six years ago.
Directed by John Varga, MD, an expert in the diagnosis, treatment, and study of scleroderma, the Northwestern Scleroderma Program provides a home for a robust clinical care and research enterprise that provides hope to the some 300,000 Americans afflicted with this orphan disease. The Program integrates world-class multispecialty clinical care with cutting-edge basic and translational research to quickly bring about patient-focused results. Recognizing that scleroderma is a disease that affects several organ systems at once, the interdisciplinary approach of the program begins with seeing patients in the clinic and extends to conducting an extraordinary range of high-impact basic science and clinical research studies.
“On the clinical side, our nationally-known rheumatologists work closely with specialists in cardiology, pulmonary medicine, and gastroenterology. Our focus is the patient as a whole,” says Dr. Varga, John and Nancy Hughes Distinguished Professor of Rheumatology. “Our research offers a depth and breadth of programs, from molecular genetics to the clinical evaluation of novel drugs.”
Pioneering Studies that Lead to Novel Therapies
The rapid pace of translating bench results to the bedside has been a hallmark of the Northwestern Scleroderma Program. For example,the recent multicenter clinical trial of the cancer drug imatinib (Gleevec®), for the prevention and treatment of skin fibrosis, resulted from the groundbreaking studies of the Varga laboratory. In their quest to understand the mechanisms of skin hardening, Dr. Varga’s research team conducted some of the earliest basic studies leading to the identification of a novel molecular pathway responsible for skin fibrosis. Along with her colleague, Monique Hinchcliff, MD, associate clinical director of the Northwestern Scleroderma Program, made a surprising discovery: they found that imatinib could potentially work to normalize this pathway and block or reduce the development of skin thickening. Preliminary clinical results show that imatinib may be beneficial for a subset of scleroderma patients with early disease. Grateful that Northwestern University Feinberg School of Medicine offers access to novel therapies, patient Amy Sandgren had the opportunity to participate in the Gleevec® trial and noticed some improvement of the skin fibrosis in her arms.
“Because scleroderma does not currently have a cure, it would be difficult for me to not try all the promising treatments that might help me and others. As a science educator, I appreciate the need for research to develop medical breakthroughs,” says Sandgren. “At Feinberg, I feel confident that I am in the right place for my care. It gives me great comfort and hope that the clinicians and staff there provide research, proactive care, and personal support for people like me who are living with scleroderma.”
Other pioneering preclinical research at Feinberg has led to the recently launched clinical trial (Phase II, open label) of dasatinib for the treatment of scleroderma lung disease. A tyrosine kinase inhibitor class of anti-cancer drug, dasatinib may be effective in reducing the scarring associated with scleroderma. One of 10 U.S. sites participating in the study, Feinberg is currently recruiting adult participants who have active scleroderma with lung involvement. Supported by a recently awarded $100,000 NIH research grant, Dr. Hinchcliff is working on the development of biomarkers to classify various types of scleroderma. Identified by analyzing gene expression in skin biopsy specimens, these biomarkers could help predict risk of internal organ involvement and treatment response to various therapies. Research findings could lead to simple screening tests, enhancing clinical decision-making regarding the selection of optimal therapies.
“The test of a good screening tool is whether it can be done by anyone,” says Dr. Hinchcliff, a prominent scleroderma clinical investigator who has won several research awards, including the first Karen Brown Scleroderma Foundation Training Award in 2006. “The beauty of this approach is that rheumatologists anywhere in the world can easily obtain skin biopsies after just 15 minutes of training.”
In fact, a skin biopsy performed at Feinberg determined that patient Renee Kane had scleroderma. She sought help from the scleroderma program after a misdiagnosis of celiac disease and a nine-month gluten-free diet didn’t take away her swelling, fatigue, and difficulty walking. Through the program, she had access to some of the innovative therapies currently under study, such as Cellcept®. “Before I came to Feinberg, I was so tired and weak that I could barely get out of bed and couldn’t do my favorite activities like play golf or volunteer,” says Kane. “Now I feel like I don’t have anything wrong with me. The scleroderma program at Feinberg saved my life.”
The Northwestern Scleroderma Program is also a clinical site for the NIH-funded multicenter Scleroderma Lung Study II (SLS II). The study compares the efficacy of the drug mycophenolate mofetil (Cellcept®) to cyclophosphamide (Cytoxan®) in the treatment of scleroderma lung disease. Feinberg also serves as a site for a collaborative, multicenter Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) study. PHAROS aims to identify risk factors and better treatments for pulmonary arterial hypertension. A clinical trial component of this study has just gotten underway to evaluate the efficacy of an oral vasodilator.
Looking to the future, Dr. Hinchcliff is spearheading the creation of an innovative Scleroderma Registry to help identify patients for clinical trials and follow disease outcomes and treatment responses. This new registry’s biorepository (serum, DNA, and skin samples) associated with clinical information will serve as a powerful tool, enabling countless research studies moving forward.
Focusing on the Whole Patient
The Northwestern Scleroderma Program serves as a strong advocate for its patients. Not only does the program provide specialized scleroderma care, but it also pays attention to the complete care of patients in areas such as dental care, alternative medicine, psychology, and occupational and physical therapy. The Program also hosts an annual Scleroderma Patient Education Day that features specialists who share the latest information with patients and their families.
James L. Schroeder, MD, past president and chief executive officer of the Northwestern Medical Faculty Foundation and current senior associate dean for External Affairs, with over 25 years of clinical experience in rheumatology, plays an instrumental part in facilitating the integration of the Scleroderma Program with other specialties at the medical school. “We’ve identified specific colleagues in disciplines we collaborate with frequently—nephrology, cardiology, pulmonary and critical care—to work with so that they develop expertise with scleroderma patients,” Schroeder says. “Data suggests that care and outcomes improve with specialization and larger numbers of patients treated for a given condition.”
The program’s faculty members also provide leadership that goes beyond Feinberg. Dr. Varga chairs the Scientific and Medical Advisory Board of the Scleroderma Foundation and serves on the Scientific Steering Committee for the International Scleroderma Research Workshop. Dr. Hinchcliff is active in the Scleroderma Clinical Trials Consortium.