Cure Research for Lupus
Research discussion: Research supported by NIAMS is looking at these issues:
- Certain genes make some people more likely to have serious
complications, such as kidney disease. NIAMS researchers have found a
gene linked to a higher risk of lupus kidney disease in African
Americans. Changes in this gene keep the immune system from removing
harmful germ-fighters from the body after they've done their job.
Other genes may also play a role.
- Lupus is more common in women than in men. Researchers are looking
into the role of hormones and other male-female differences.
- One NIAMS project is testing a new drug that scientists hope will have milder side effects than standard treatments. Another study is testing a combination of two medicines. One is a standard drug and the other is a new drug. Scientists hope that the combination will be more effective and cause fewer side effects.
Lupus is the focus of intense research as scientists try to determine what causes the disease and how it can best be treated. Some of the questions they are working to answer include: Exactly who gets lupus, and why? Why are women more likely than men to have the disease? Why are there more cases of lupus in some racial and ethnic groups? What goes wrong in the immune system, and why? How can we correct the way the immune system functions once something goes wrong? What treatment approaches will work best to lessen or cure lupus symptoms?
To help answer these questions, scientists are developing new and better ways to study the disease. They are doing laboratory studies that compare various aspects of the immune systems of people with lupus with those of other people both with and without lupus. They also use mice with disorders resembling lupus to better understand the abnormalities of the immune system that occur in lupus and to identify possible new therapies.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a component of the National Institutes of Health (NIH), has a major program of lupus research in its intramural program in Bethesda, Maryland, and funds many individual researchers across the United States who are studying lupus. To help scientists gain new knowledge, the NIAMS also has established Specialized Centers of Research devoted specifically to lupus research. In addition, the NIAMS is funding several lupus registries that will gather medical information as well as blood and tissue samples from patients and their relatives. This will give researchers across the country access to information and materials they can use to help identify genes that determine susceptibility to the disease.
Identifying genes that play a role in the development of lupus is an active area of research. For example, researchers suspect a genetic defect in a cellular process called apoptosis, or "programmed cell death," in people with lupus. Apoptosis is similar to the process that causes leaves to turn color in autumn and fall from trees; it allows the body to eliminate cells that have fulfilled their function and typically need to be replaced. If there is a problem in the apoptosis process, harmful cells may stay around and do damage to the bodyís own tissues. For example, in a mutant mouse strain that develops a lupus-like illness, one of the genes that controls apoptosis is defective. When it is replaced by a normal gene, the mice no longer develop signs of the disease. Scientists are studying what role genes involved in apoptosis may play in human disease development.
Studying genes for complement, a series of proteins in the blood that play an important part in the immune system, is another active area of lupus research. Complement acts as a backup for antibodies, helping them destroy foreign substances that invade the body. If there is a decrease in complement, the body is less able to fight or destroy foreign substances. If these substances are not removed from the body, the immune system may become overactive and begin to make autoantibodies.
Recent large studies of families with lupus have identified a number of genetic regions that appear to confer risk of SLE. Although the specific genes and their function remain unknown, intensive work in delineating the entire human genome offers promise that these genes will be identified in the near future. This should provide knowledge of the fundamental nature of the risk factors that can lead to lupus and new insights into how these risks can be modified.
It is thought that autoimmune diseases, such as lupus, occur when a genetically susceptible individual encounters an unknown environmental agent or trigger. In this circumstance, an abnormal immune response can be initiated that leads to the signs and symptoms of lupus. Research has focused on both the genetic susceptibility and the environmental trigger. Although the environmental trigger remains unknown, microbial agents such as Epstein-Barr virus and others have been considered. Researchers also are studying other factors that may affect a personís susceptibility to lupus. For example, because lupus is more common in women than in men, some researchers are investigating the role of hormones and other male-female differences in the development and course of the disease.
A current study funded by the NIH is focusing on the safety and effectiveness of oral contraceptives (birth-control pills) and hormone replacement therapy in women with lupus. Doctors have worried about the wisdom of prescribing oral contraceptives or estrogen replacement therapy for women with lupus because of a widely held view that estrogens can make the disease worse. However, recent limited data suggest these drugs may be safe for some women with lupus. Researchers hope this study will yield options for safe, effective methods of birth control for young women with lupus and enable postmenopausal women with lupus to benefit from estrogen replacement therapy.
Promising Areas of Research
Researchers are also focusing on finding better treatments for lupus. A primary goal of this research is to develop treatments that can effectively minimize the use of corticosteroids. Scientists are trying to identify combination therapies that may be more effective than single-treatment approaches. Researchers are also interested in using male hormones, called androgens, as a possible treatment for the disease. Another goal is to improve the treatment and management of lupus in the kidneys and central nervous system. For example, a 20-year study supported by the NIAMS and the NIH found that combining cyclophosphamide with prednisone helped delay or prevent kidney failure, a serious complication of lupus.
On the basis of new information about the disease process, scientists are using novel "biologic agents" to selectively block parts of the immune system. Development and testing of these new drugs, which are based on compounds that occur naturally in the body, comprise an exciting and promising new area of lupus research. The hope is that these treatments not only will be effective, but also will have fewer side effects. Other treatment options currently being explored include reconstructing the immune system by bone marrow transplantation. In the future, gene therapy also may play an important role in lupus treatment. 2
Researchers are looking at how genetic, environmental, and hormonal factors influence the development of systemic lupus erythematosus. They are trying to find out why lupus is more common in certain populations. There has been very promising progress in identifying the genes that may be responsible for lupus. Promising areas of treatment research include biologic agents; newer, more selective drugs that suppress the immune system; and efforts to correct immune abnormalities with bone marrow transplantation. Clinical studies are underway to determine the safety of estrogens for hormone replacement therapy and birth control in women with lupus. Contrary to the widely held belief that estrogens can make the disease worse, recent data suggest that these drugs may be safe for some women with lupus.3
Medical research for Lupus: medical news summaries: The following medical news items are relevant to medical research for Lupus:
- Arthritis Foundation reports on top 10 arthritis developments in 2004
- Compound related to anti-anxiety drugs may provide an effective treatment for psoriasis
- Protein biomarkers for lupus have been identified
- Women with lupus more prone to abnormal pap smears
1. excerpt from The Many Shades of Lupus: NIAMS
2. excerpt from Handout on Health Systemic Lupus Erythematosus: NIAMS
3. excerpt from Questions and Answers About Arthritis and Rheumatic Diseases: NIAMS
Last revision: June 2, 2003
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