Drug Might Restore Sense of Smell

July 11, 2009 -- A drug once used to treat asthma and other respiratory conditions shows promise in restoring a sense of smell to those who have lost that precious ability.

"More work needs to be done but, for patients for whom other treatments don't work, this may be an option worth trying," said Dr. Ronald Kuppersmith, clinical assistant professor of surgery at Texas A&M Health Science Center College of Medicine and president-elect of the American Academy of Otolaryngology-Head and Neck Surgery.

The drug, theophylline, does have side effects and is now out of vogue for asthma and related disorders, said Kuppersmith, who was not involved in the study.

According to background information in the article, about 20 million people in the United States have some degree of hyposmia, or loss of the sense of smell, affecting their ability to enjoy the flavor of artichokes and the fragrance of azaleas.

"There's a whole spectrum from having mild changes in your sense of smell to complete loss," Kuppersmith said. "It can be very frustrating for the patient, but also for the physician. A lot of people can't enjoy coffee because they can't smell it. They lose weight. They can't smell flowers."

Any number of things can cause the problem. "The most common causes are viruses, head trauma, severe allergies or some kind of anatomic obstruction in the nose or nasal polyps," Kuppersmith explained.

In June, U.S. health officials warned consumers to stop using Zicam nasal cold remedy products because they can cause the loss of a sense of smell.

According to Dr. Robert Henkin, lead author of the study that appears in the June issue of the American Journal of the Medical Sciences, there are few effective treatments out there.

Henkin, director of the Center for Molecular Nutrition and Sensory Disorders in Washington, D.C., and his colleagues had previously discovered that people with hyposmia had reduced levels of cyclic nucleotides in their saliva and nasal mucous, and that treatment with theophylline had increased levels of this growth factor and restored some of the sense of smell.

These cyclic nucleotides are growth factors for olfactory (related to smell) and other neural tissues.

"I had earlier done the first total protein analysis of saliva and mucous to learn what was in there, and found these growth factors and found that people who couldn't smell had diminished levels of the factors," Henkin explained. "Theophylline, in a sense, inhibits the breakdown of growth factors so more are going to stick around."

Henkin and his team have now confirmed the efficacy of theophylline in this context in 312 patients with hyposmia over a seven-year study period.

All of the study participants had decreased levels of growth factors cAMP and/or cGMP, as measured in their nasal mucous.

More than half of participants said their sense of smell improved after being treated with theophylline, while more than 20 percent said their smell returned to normal. Larger doses of the compound and longer treatment times resulted in greater improvements.

"People who had relatively mild or moderate disease seemed to respond to this treatment but those patients tend to respond to other treatments as well," Kuppersmith said. "Most of those who had severe or complete loss of sense of smell didn't respond, which is typical of a lot of treatments out there."

Also, he said, "some people who lose their sense of smell get better anyway, especially if they have mild cases, so they would have gotten better with or without treatment."

But, Kuppersmith added, for certain patients this might be a helpful option if other things don't work.

Side effects of theophylline were minimal, the researchers noted, but can include jitteriness, nervousness and difficulty falling asleep.

Henkin said that the findings need to be verified with a clinical trial. His team is now looking at ways to deliver the drug intranasally (this study involved pills). He also needs a drug company to develop and market the medication, should it continue to prove useful.

More information

The Sense of Smell Institute has more on hyposmia.

SOURCES: Robert I. Henkin, M.D., Ph.D., director, Center for Molecular Nutrition and Sensory Disorders, Washington, D.C.; Ronald Kuppersmith, M.D., clinical assistant professor, surgery, Texas A&M Health Science Center College of Medicine, otolaryngologist, Texas ENT and Allergy, College Station, and president-elect, American Academy of Otolaryngology-Head and Neck Surgery; June 2009, American Journal of the Medical Sciences