Unlocking Mysteries of the Immune System May Be the Key in Curing Inflammatory DiseaseA 10-year-old student, instructed by the school nurse to not come back to school, because of his psoriasis.
A young mother, disabled by multiple sclerosis, forced to use a cane where she once strolled freely.
An esteemed university chemistry professor, unable to grasp the tools so vital to teaching his craft because of rheumatoid arthritis.
For all three, each day is a struggle against bodies that have turned against them. The natural process of inflammation, normally enacted to repair tissue and fight infection, has gone awry, attacking the skin, central nervous and musculoskeletal systems, respectively. As a result, the boy lives with scaly, red patches of skin which, though not contagious, make adults shy away and prompt his classmates to tease him mercilessly. The mother battles relapses of fatigue and loss of balance which appear without warning and outstay their welcome. And the professor, who teaches through the painful swelling in his hands, lives from bottle to bottle of nonsteroidal anti-inflammatory agents.
“For years, a group of chronic, inflammatory diseases has frustrated physicians and patients seeking effective treatment,” says Cecil B. Wilson, M.D., an internist in Winter Park, Fla. and an American Medical Association (AMA) trustee. “The growing body of knowledge about the immune system’s role in diseases such as psoriasis, rheumatoid arthritis, myasthenia gravis, scleroderma and multiple sclerosis (MS) means that there is hope for long-term treatments and perhaps even cures.”
In light of such recent discoveries, the AMA held an inflammatory diseases media briefing in New York City, where experts gathered to discuss the evolving body of thought surrounding the treatment of these chronic autoimmune diseases which, as of now, have no cure.
“All of these disorders are chronic progressive diseases,” says Anthony Gaspari, M.D., a dermatology expert from the University of Maryland in Baltimore and a speaker at the AMA media briefing. “Unlocking the secrets of some might lead to therapies for others.” For example, he said, while the immune system has long been implicated in MS, “it has only been in the last five years or so that we’ve believed that the immune system plays a role in psoriasis.”
New Biologic Treatments Offer Hope
Although many inflammatory diseases seem to have a genetic component, some are triggered by other processes. Cytokines, for instance, are naturally-produced proteins that trigger inflammatory and disease-fighting responses to toxins, injury, viruses and bacteria. These proteins are of particular interest when studying inflammatory disorders, Gaspari says, as their malfunction may be responsible for everything from the over-production of skin in psoriasis to the destruction of nerve insulating material in MS to the abnormal growth of connective tissue in scleroderma.
Psoriasis, which affects up to 7 million men and women, serves as a particularly good bench-to-bedside example of how scientific discoveries are making their way from the lab into clinical practice. While the exact cause of psoriasis is not known, experts do know that symptoms are a result of cells in the outer layer of the skin reproducing quickly and piling up on the skin’s surface. Although certain cases are limited to areas such as the elbows, knees and scalp, others can involve anywhere from 10 to 100 percent of the body.
For those patients who suffer from more aggressive cases, new biologic agents offer an alternative in treating psoriasis, said Kenneth B. Gordon, M.D., associate professor of medicine in the division of dermatology at Loyola University Medical Center in Maywood, Ill. Designed through genetic engineering to affect only the target organ system -- in this case the immune system and the skin -- biologic therapies avoid the multiorgan toxicity often seen with traditional treatments such as methotrexate and cyclosporine. Biologics are delivered via injection rather than orally, because the proteins would be broken down in the stomach, and improvements are typically seen after a couple of months of twice-a-week to every-other-week treatment.
The first biologic for the treatment of psoriasis was approved by the Food and Drug Administration in February 2003; others are being looked at for potential use. These agents, Gordon says, may help more patients in returning to normal lives.
“Many patients no longer seek healthcare for this condition because they believe their options are exhausted and they must live with the disease,” Gordon explains. “They are frustrated with therapy because their physician doesn’t think their condition merits aggressive therapy or doesn’t understand the therapies that are available. People who have given up hope need to know that there are new treatments available.” And while therapies such as specific alteration in gene expression are on the distant horizon, for now, Gordon believes, “biological agents are the future for the next decade or beyond.”
Optimistic Future for Patients
In MS, a life-long chronic disease affecting 250,000 to 300,000 Americans, the disease attacks random patches of the central nervous system’s white matter, causing partial destruction of myelin, the substance which insulates the nerve fibers of the brain and spinal cord. Initial symptoms are often vision-related, such as blurred or double vision, distortion of red and green, or blindness in one eye. Muscular weakness, loss of coordination or balance, numbness or pain, fatigue and slurred speech typically follow. Studies show that the aforementioned cytokines may cause this abnormal autoimmune response and influence myelin damage.
Standard therapy has included corticosteroids to suppress the immune system. But now, for the first time, people with MS have a choice of several biologically-based anti-inflammatory treatments to effectively modify the course of their disease. New biologic agents such as beta-interferons are immunomodulatory -- not immunosuppressive -- in nature, halting MS inflammation by repairing the blood-brain barrier and reducing the inflammatory process. Depending on the beta-interferon prescribed, patients may experience decreased relapse rates, increased time between relapses, decreased attack severity and a reduced number of MS lesions.
“Patients should be very optimistic about the long-term outlook for multiple sclerosis,” says AMA media briefing speaker Brian R. Apatoff, M.D., director of Multiple Sclerosis Clinical Care and Research Center at New York-Weill Cornell Medical Center in New York City. “Twenty years ago there weren’t really any treatments for MS, we were fumbling around with corticosteroids as the mainstay in immune intervention. Now we have become more sophisticated and developed new therapies which have fewer side effects than steroids but still control the inflammation.”
Multiple sclerosis patients aren’t the only ones who should be feeling optimistic about their diagnosis. For although there is currently no cure for any of these diseases, the future looks promising. “As we unravel the mysteries of the immune system and identify the genes that are passed on in families,” Gaspari says, “we may be able to develop therapies that can be used long-term or that actually cure these disorders.”
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