How Come We Can't Cure the Cold?

By

this point, nobody needs a refresher course on the symptoms of the common cold. With just one more month left in peak cold season, most folks have already suffered their share of scratchy throats, runny noses, raucous sneezes and nagging headaches. If only the changing weather meant you were out of harm's way. Alas, colds are caused by hundreds of different viruses from several major viral families. Spring turns out to be prime time — along with summer and fall — for the so-called rhinoviruses, culprits in as many as 35% of all colds. There's just no time of year when some type of cold virus can't get you.

Besides making sufferers miserable, colds are also more of a drain on the economy than most of us realize. A study from the University of Michigan, published in last week's Archives of Internal Medicine, estimates that colds cost the U.S. $40 billion a year — more than the tally for osteoporosis or congestive heart failure. "If anything, that number is probably on the low side," says Dr. Mark Fendrick, who led the study. He notes that earlier estimates, which had put the cold burden at $5 billion to $10 billion, did not account for, among other things, the fact that parents often stay home from work to care for their ailing children.

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It wasn't supposed to be this way. When researchers published their first highly detailed analysis of the structure of a human rhinovirus back in 1985, it was easy to imagine that a cure for the common cold might soon be available. After all, once scientists discovered which molecular footholds rhinoviruses use to latch onto and infect human cells, it should not have been that hard to develop a drug that would block the linkage and cure a cold before it got started. Or so the thinking went. Unfortunately, the logistics, from both a biological and a business point of view, turned out to be a lot more complicated than anyone expected. The crash of the biotech sector, in which some of the more interesting anticold research has taken place, certainly didn't help.

First, the biology. Doctors pretty quickly gave up on the idea of developing one vaccine to prevent all common colds. There are just too many kinds of cold viruses to make that a practical approach, which leaves us treating our colds after they have already started. But here's the rub. Researchers know that most of the symptoms we associate with getting a cold — the runny nose, the congested sinuses — are caused not by the cold virus but by the body's attempts to clear the virus. It turns out that our body's immune system automatically tries several strategies to counter the virus — some more effective than others. Most of the suffering can be traced back to the so-called inflammatory response, which actually does nothing to beat the cold virus.

Indeed, the viral attack is practically over within the first couple of days of a cold, often before you realize that anything is wrong. To be effective, an antiviral cold drug would have to be taken as soon as you suspect you might be coming down with something. That's a tall order but not impossible. In the mid-1990s the German drug company Boehringer-Ingelheim developed an antiviral molecule, dubbed birr 4, that proved in clinical trials to significantly shorten most colds triggered by rhinoviruses and lessen their severity. The product worked by mimicking those molecular footholds used by rhinoviruses to gain entry into human cells. Spraying the nasal passages every few hours on the first day of a cold essentially fooled the virus into leaving the cells alone.

Sounds like a blockbuster drug, right? Wrong. Here's where those pesky business considerations come in. Once Boehringer's executives started doing the math, they quickly realized that BIRR 4 was not commercially viable. Its modest therapeutic effects, combined with the need to provide the drug so early in the infection process, severely limited its marketability. Two and a half years ago, Boehringer dropped further development of BIRR 4.

Another antiviral drug, called pleconaril, had the rug pulled out from under it last March when the U.S. Food and Drug Administration declined to approve it, citing concerns that pleconaril might interfere with the effectiveness of oral contraceptives and other drugs. To combat that problem, Viropharma, the biotech company that developed pleconaril, decided to reformulate the pill, turning it into a nasal spray, thereby lowering its dose and the chance that it might interfere with other drugs. Viropharma is now looking for another pharmaceutical company to help defray the costs of testing the new formula.

Of course, even if an effective antiviral drug is eventually developed, that takes care of only part of the problem. "You have to do more than just stop the virus," says Dr. Jack Gwaltney of the University of Virginia School of Medicine in Charlottesville. "You need to block these inflammatory processes too." Intriguingly, Gwaltney, who has studied the common cold for more than 40 years, has shown that although it's easy to become infected with a cold virus, about 25% of those who get infected suffer few if any symptoms. For whatever reason, their bodies do not go overboard fending off a viral attack. That suggests to him that you ought to be able to stop the virus and damp down the immune system without causing any major side effects and that any cure has to consist of a combination of drugs.