An End To The Misery?

AS ANY IMMUNOLOGIST WILL TELL YOU, ALLERGIES are nothing to sneeze at. At least 40 million Americans suffer the effects, which range from itchy eyes to shock and death. Hay fever alone prompts 8 million doctor visits every year, while asthma claims 4,000 lives and costs the nation $8 billion in treatment and lost wages. Medical science has never gotten much beyond treating the symptoms, but that could soon change. "We are no longer going to just treat asthma and allergic rhinitis," says Dr. John Selner, director of the Allergy Respiratory Institute in Denver. "We're going to technologically alter those diseases."

Like a dog that chases cars, an allergy-prone immune system doesn't save its wrath for malevolent intruders. It responds to harmless foreign substances by producing potent antibodies known as IgE. The reaction involves several steps. When an allergen enters the body, so-called helper T cells signal danger by releasing a chemical called Il-4. That alarm prompts a second class of immune cells--the B cells--to churn out IgE antibodies. When these antibodies dock with receptors on still other immune cells (the mast cells and basophils), they trigger a flood of histamine and other chemicals. These "allergic mediators" cause different kinds of misery depending on the tissues they infiltrate.

How could science reverse such a process? One approach, pioneered by researchers at Genentech of South San Francisco and Tanox Biosystems of Houston, is to knock out IgE with genetically engineered antibodies. Both firms have designed molecules that fit onto IgE as a lock fits around a key. By binding with IgE before it can connect with the receptors on mast cells, these agents should prevent the release of histamine. Both companies have completed initial safety studies and are now giving patients injections to gauge the therapeutic effects. If all went well, a drug could reach the market within seven years.

Meanwhile, scientists at Palo Alto's DNAX Research Institute are learning to defuse allergic reactions at an even earlier stage. Reasoning that errant B cells would make less IgE if they weren't always being goaded by Il-4, the DNAX researchers have created an impotent version of the Il-4 molecule. Given to mice, the molecule sticks to the receptors on B cells, shutting out true Il-4 and foiling IgE production. The mouse study was intended merely to highlight Il-4's role in IgE synthesis. But its results suggest that dummy Il-4 could make potent medicine.

Even if these methodical endeavors don't revolutionize allergy treatment, trial and error just might. Consider what happened when researchers at Chicago's Northwestern University Medical School started studying a natural hormone called substance P. As expected, a single dose made animals more sensitive to a common allergen. But several months later, Dr. Roy Patterson discovered that the treated animals were producing fewer allergic antibodies. Suspecting he was onto something, Patterson treated three colleagues with substance P and small doses of ragweed or rye grass. Before they got the treatment, all three were producing IgE antibodies to those irritants, though not enough to cause symptoms. After their shots, two of the three experienced a sharp drop in IgE, and the effect has persisted. Larger studies are now in the works.

Don't toss your Kleenex just yet; sparkling preliminary findings rarely turn out to be gold. But if these new approaches pan out, they could yield a mother lode of relief.

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