Cure for the Common Cold? Not Yet, but Possible

http://www.nytimes.com/2009/02/13/health/research/13cold.html

February 13, 2009
Cure for the Common Cold? Not Yet, but Possible
By NICHOLAS WADE

Curing the common cold, one of medicine’s most elusive goals, may now be in the realm of the possible.

Researchers said Thursday that they had decoded the genomes of the 99 strains of common cold virus and developed a catalog of its vulnerabilities.

“We are now quite certain that we see the Achilles’ heel, and that a very effective treatment for the common cold is at hand,” said Stephen B. Liggett, an asthma expert at the University of Maryland and co-author of the finding.

Besides alleviating the achy, sniffly misery familiar to everyone, a true cold-fighting drug could be a godsend for the 20 million people who suffer from asthma and the millions of others with chronic obstructive pulmonary disease. The common cold virus, a rhinovirus, is thought to set off half of all asthma attacks.

Even so, it might be difficult to kindle the interest of pharmaceutical companies. While the new findings are “an interesting piece of science,” said Dr. Glenn Tillotson, an expert on antiviral drugs at Viropharma in Exton, Pa., he noted that the typical cost of developing a new drug was now $700 million, “with interminable fights with financiers and regulators.”

Because colds are mostly a minor nuisance, drug developers say, people would not be likely to pay for expensive drugs. And it would be hard to get the Food and Drug Administration to approve a drug with any serious downside for so mild a disease.

Carl Seiden, president of Seiden Pharmaceutical Strategies and a longtime industry analyst and consultant, said industry might be loath to wade in because Relenza and Tamiflu — two drugs that ameliorated flu but did not cure it — were huge commercial disappointments.

The industry has also learned in recent years that turning a genetic discovery into a marketable drug is far harder than once thought.

Still, if the discovery could lead to an effective drug to treat the common cold, “that’s a big deal,” Mr. Seiden said.

Industry hurdles aside, perhaps the biggest reason the common cold has long defied treatment is that the rhinovirus has so many strains and presents a moving target for any drug or vaccine.

This scientific link in this chain of problems may now have been broken by a research team headed by Dr. Liggett and Dr. Ann C. Palmenberg, a cold virologist at the University of Wisconsin.

The researchers, who conducted the genetic decoding with the aid of Dr. Claire Fraser-Liggett at the University of Maryland, published their insights into the rhinovirus on Thursday in the online edition of Science.

Dr. Fernando Martinez, an asthma expert at the University of Arizona, said the new rhinovirus family tree should make it possible for the first time to identify which particular branch of the tree held the viruses most provocative to asthma patients.

If antiviral agents could be developed against this group of viruses, Dr. Martinez said, “it would be an extraordinary advance.”

Another asthma expert, Dr. E. Kathryn Miller at the Vanderbilt Children’s Hospital in Nashville, said the new finding was “a groundbreaking study of major significance.”

People at high risk from rhinoviruses, like children with asthma or adults with chronic obstructive pulmonary disease, would benefit greatly from new drugs, Dr. Miller said, and should therefore be populations of interest to the drug industry.

Dr. Liggett said the new data might even provide an opportunity to consider new vaccine approaches.

Dr. Palmenberg is less optimistic. “There’s not going to be a vaccine for the common cold,” she said, given that vaccines do not protect the linings of the nose where the virus attacks.

The rhinovirus has a genome of about 7,000 chemical units, which encode the information to make the 10 proteins that do everything the virus needs to infect cells and make more viruses.

By comparing the 99 genomes with one another, the researchers were able to arrange them in a family tree based on similarities in their genomes.

That family tree shows that some regions of the rhinovirus genome are changing all the time but that others never change.

The fact that the unchanging regions are so conserved over the course of evolutionary time means that they perform vital roles and that the virus cannot let them change without perishing. They are therefore ideal targets for drugs because, in principle, any of the 99 strains would succumb to the same drug.

Dr. Liggett said he believed that one such target lies at the very beginning of the rhinovirus genome, where its genetic material is folded into a clover-leaf shape. The sequence of units in the clover leaf is designed to be read quickly by the infected cell’s protein-making machinery. All strains of rhinovirus have much the same sequence of units at this region and all could be vulnerable to the same drug.

The data will also help analyze a new family of rhinoviruses that is causing concern. Instead of attacking the cells lining the nose, these attack those lining the deep lungs, causing viral pneumonia.

This family of virus cannot at present be grown for study in the laboratory, Dr. Palmenberg said, but can now be researched genetically through the common elements they share with other rhinoviruses.

Researchers at the J. Craig Venter Institute, where the rhinovirus genomes were decoded, say another important feature of the viruses lies in a highly variable region at one of the genomes.

The equivalent region in polio virus determines pathogenicity, and the same may be true with rhinoviruses.

There are at present no effective treatments for the common cold. Frequent hand-washing is the best preventive, Dr. Miller said. Once a cold has started, she recommended washing out the nasal passages, warm drinks and rest.

Gardiner Harris contributed reporting from Washington.