LUPUS RESEARCH ALLIANCE SPONSORS THE 2017 FORUM FOR DISCOVERY: FRONTIERS IN IMMUNE REGULATION
Visionary Scientists and Industry Leaders Report on Promising Advances and Future Directions in Lupus Research
Nov. 16, 2017. Last month, 150 dedicated research scientists, pharmaceutical industry representatives, and Lupus Research Alliance advocates met in New York City at the 2017 Forum for Discovery, the Alliance’s annual scientific conference. Welcoming participants, Kenneth M. Farber, President and CEO of the Lupus Research Alliance, noted that “everything we are able to accomplish relies on the terrific scientific visionaries who are allies in our passionate support of lupus research.”
At the forefront of the meeting was the pursuit of innovative, targeted research that will improve the lives of all individuals living with lupus. Scientists described their most up-to-date research, while the rich scientific discussions at the Forum served as an incubator to spark ideas for new research directions. Our corporate partners added a deep knowledge of drug development, essential for translating scientific discoveries into new treatments. Among the many exciting advances in lupus research described at the Forum, attendees were pleased to hear from four distinguished keynote and guest lecturers:
New Frontiers in Disease Prediction
Kenneth Smith, FRACP, PhD, FMedSci, Professor and Head of Medicine at University of Cambridge in the United Kingdom, studies how the healthy immune system works and how it breaks down in autoimmune diseases, including lupus. A major focus of his research is to identify biomarkers or signals that can predict the course of a disease, so treatment can be tailored to the patient.
In one pioneering clinical study of lupus biomarkers, Dr. Smith and his team recruited a group of 26 individuals with active lupus. He divided the patient volunteers into two groups depending on how their patterns of gene activity were in certain T cells of the immune system. These gene patterns, which he called “8.1” and “8.2,” are like two different paths on a map—both paths will lead to a destination, but with very different experiences. Likewise, both the 8.1 and the 8.2 gene patterns are associated with T cells that can function properly to fight off infectious or abnormal cells, but T cells with an 8.1 pattern might act slightly differently than those with an 8.2 pattern. After 500 days, Dr. Smith found that 100% of the study volunteers with an 8.1 pattern had experienced at least one lupus flare, whereas only 15% of the volunteers with an 8.2 pattern had had a flare. Even after 1,000 days, 70% of the 8.2 group was still free of new flares.
Dr. Smith is now looking for ways to develop a simple blood test that can similarly distinguish individuals who are more likely to experience flares from those with a milder disease course.
Innovative Clinical Trials to Bring Safe and Effective New Drugs to Patients
Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), spoke about innovative clinical trial designs that are allowing new pharmaceutical drugs to reach doctors and patients as quickly as possible. The biomedical research field has exploded in recent years with fascinating insights into the causes of many diseases, including lupus. But the process of translating those insights into real therapies for patients can take many years, requiring vast amounts of money and effort. Indeed, only one new drug designed specifically for lupus has been approved in the modern era.
Dr. Woodcock had valuable advice for lupus scientists who are thinking about how to turn their research results into new treatments. First, she stressed the importance of research to fully understand the natural history of lupus and its complications. For example, what are the signals (biomarkers) that predict who is going to have more mild or more severe symptoms? How can individuals with lupus be sorted into groups with similar symptoms or patterns of flares or by their risk of developing specific complications, such as kidney disease? Knowing which subsets of patients are most likely to benefit from a potential new drug would speed up clinical trials and FDA approval of new drugs. Next, Dr. Woodcock noted that an in-depth understanding of the molecular pathways of disease development and progression is essential to designing very specific drugs to treat a disease like lupus. Lupus researchers need to map out a more complete blueprint of the immune system in individuals with and without lupus. This blueprint would help them hone in on the specific problems in the immune system that cause lupus, thus assisting researchers to develop more effective, targeted drugs that can be tested in well-designed, faster, and less expensive clinical trials for the benefit of all lupus patients.
Developing New Medicines in Immune Disease: Getting It Right
Thomas O. Daniel, MD, Chairman and President of Vividion Therapeutics and a member of the Lupus Research Alliance Board of Directors, relayed a story of how rigorous scientific and clinical investigation turned one of the saddest chapters in medical science into new hope for patients with leprosy, AIDS, cancer, and now, lupus.
In the 1950s, the drug thalidomide was used outside of the United States to combat morning sickness in pregnant women, but the drug caused severe birth defects. Scientists continued studying how thalidomide works and found that it blocks a key molecule of the immune system, making the drug a highly effective treatment for leprosy, complications of AIDS, and certain cancers. Knowing how thalidomide affects the immune system, researchers at Celgene Corporation, where Dr. Daniel previously served as Chairman of Research, and then were able to create entirely new drug candidates that target the same immune system molecule, yet do not cause birth defects. One of those drug candidates “CC-220” is now in clinical trials for lupus.
Controlling Long-Term Survival of Plasma B Cells
David M. Tarlinton, PhD, Professor and Head of Immunology and Pathology at Monash University in Australia, investigates the biology of long-lived plasma cells of the immune system. Plasma B cells are one of the memory cards of the immune system. After a generic B cell runs into a foreign invader—bacteria or viruses, for example—the cell matures further into a plasma B cell or plasma cell for short and makes highly specific antibodies to fight that particular invader. A plasma cell can live for years in the body, remembering its target and ready to jump into action if the same infection ever comes back. In lupus and other autoimmune diseases, the long life and memory of plasma cells is a disadvantage. Some plasma cells go rogue and make antibodies against parts of a person’s own body, such as DNA, a molecule at the heart of nearly every cell in the body. These plasma cells may contribute to more severe disease or faster disease progression. In a series of innovative experiments, Dr. Tarlinton identified a complex network of genes that affect the survival and activity of plasma cells. His work provides a solid foundation for the development of new, targeted strategies to improve therapies that eliminate plasma B cells in lupus patients. Ideally, the next generation of B cell depletion therapies will eliminate only those plasma cells that produce lupus-related antibodies, leaving the healthy parts of the immune system intact.