When Dr. Edgar Engleman began studying DHEA, a human hormone secreted by the adrenal gland, all he knew was that it might affect the immune system.
He and his Stanford University colleagues had noticed that the hormone prompted white blood cells, the foot soldiers of the immune system, to produce more of an infection-fighting protein, interleukin-2. There had to be some way, they thought, of harnessing DHEA's powers to combat disease.
Engleman scoured the scientific literature, searching for a condition that might respond to this hormone -- and found that lupus sufferers were deficient in both DHEA and interleukin-2. "We thought the apparent lack of this hormone may be important in how the disease gets caused," says Engleman, an immunologist in the Stanford University School of Medicine in Palo Alto. "There was also a fairly strong circumstantial case that replacing the hormone would be beneficial."
That was more than a decade ago. Now a synthetic version of the hormone is expected to become the first new drug for treating lupus in more than 30 years. Called Prestara, the oral medication seems to ease symptoms without the harmful side effects of current treatments.
Systemic lupus erythematosus, commonly called SLE or lupus, afflicts about 200,000 Americans, 90% of whom are women. It is an often debilitating disease in which the body's immune system stops working properly. Instead of fighting off germs and disease, it attacks healthy tissue, causing joints, skin, muscles and vital organs, such as the kidneys, heart and nervous system, to become painfully swollen and inflamed. Common symptoms, which can wax and wane, include pain, fever, skin rashes, sensitivity to sunlight, headaches, high blood pressure, swelling in the feet and legs, and an overwhelming fatigue.
Chronic sufferers can also develop severe osteoporosis, the bone-thinning condition that makes people prone to hip, spine and wrist fractures. And lupus can be fatal; 20% of patients die within 10 years of diagnosis, usually from kidney damage or heart disease.
Existing treatments, such as steroids to ease inflammation, are of limited benefit and often cause other problems. "For people with mild to moderate lupus, this drug will be a real breakthrough because it reduces symptoms without adverse effects," says Dr. Michelle A. Petri, a lupus expert at Johns Hopkins University in Baltimore.
In 1993, after the Stanford scientists decided to focus on lupus, they did a pilot study with 10 patients who were given daily doses of DHEA. The response was encouraging. "The majority of patients felt substantially better. They didn't have flare-ups, they reduced their use of steroids, and they seemed to recover a tremendous amount of energy," Engleman says.
Subsequent research yielded similar results. A 1997 study of 191 women who had lupus found that, by using Prestara, they were able to significantly cut their intake of steroids. In a 1999 study of 381 women, half of whom received Prestara and half of whom were given a placebo, the Prestara group had a 35% better response than the placebo group in terms of lifting fatigue, stabilizing disease and alleviating symptoms.
In the later study, researchers also observed that the drug seems to harden bones. Tests are currently underway on 150 women at 20 centers around the country to confirm whether Prestara does increase bone mineral density. The Food and Drug Administration issued a conditional approval of the drug in 2002, contingent upon the outcome of these tests.
Genelabs Technologies Inc., a Redwood City, Calif., company that makes Prestara, hopes to have the drug available for sale by the end of 2004. "It will be unbelievably satisfying to me if this does make it to market," says Engleman, "and starts helping patients."
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Risks of standard treatments
For milder lupus cases, doctor often recommend over-the-counter pain relievers, such as acetaminophen (Tylenol) and ibuprofen (Motrin, Advil) or prescription anti-inflammatory drugs, such as naproxen (Naprosyn) and Cox 2 inhibitors (Vioxx, Celebrex), to reduce the pain and swelling of joints and decrease stiffness and inflammation.
But chronic use of most of these medications can accelerate joint breakdown and cause intestinal bleeding. Anti-malarial medications, such as chloroquine (Aralen) and hydroxychloroquine (Plaquinil), can ease fatigue, skin rashes and joint pain, though habitual use can upset the stomach.
For more severe symptoms, oral corticosteroid drugs (Prednisone) are used to dampen the haywire immune response that triggers lupus symptoms. However, long-term use of steroids can cause serious side effects, including cataracts, high blood pressure, weight gain, muscle loss and severe depletion of bone mineral density, which exacerbates the osteoporosis that plagues lupus patients.