Treatment With Theophylline Improves Smell Function When Biochemistry Is The Culprit

Main Category: Ear, Nose and Throat
Also Included In: Neurology / Neuroscience;  Biology / Biochemistry;  Conferences
Article Date: 08 Apr 2008 - 7:00 PST

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Despite the fact that millions of Americans are believed to have lost their sense of smell (hyposmia), no effective method exists to treat many of these people. That is due in part to the fact that the causes of smell loss are varied and complex, ranging from chronic allergies, viral infection, head injury, or no apparent reason at all. Some seven percent of Americans have lost their sense of smell and with it their ability to enjoy the fragrance of flowers, foods and beverages. For individuals whose smell loss relates to the biochemistry of two common proteins, there is some good news. A team of researchers has found that a drug used long ago to help asthmatics can benefit some with smell loss.

The Study

The results are contained in a study entitled Effective Treatment of Smell Loss With Theophylline. It was conducted by Robert I. Henkin, Irina Velicu and Loren Schmidt all of the Taste and Smell Clinic, Center for Molecular Nutritional Sensory Disorders, Washington, DC. Dr. Henkin will present his team's findings at the 121st annual meeting of the American Physiological Society, part of the Experimental Biology 2008 scientific conference.

A total of 369 individuals were enrolled in the study. Of the total, 314 had smell loss and 55 did not; 169 were female and 145 were male. The participants were 53 years of age ± 1 year. Smell loss was measured using standard testing procedures to determine the type, degree and character of smell loss. These included objective smell function (psychophysical) and subjective (quantitative evaluation of smell loss) methods. Blood measures and smell function were evaluated regularly throughout the study.

The researchers had previously discovered that decreased levels of two proteins - cyclic AMP (cAMP) and cyclic GMP (cGMP) - in nasal mucus inhibited growth and development of olfactory receptor cells and thus caused smell loss. For this reason, patients consumed 200, 400 or 600 mg of theophylline (correlated to blood levels) for a period of 2-6 months.

The drug theophylline is a generalized phosphodiesterase inhibitor. Physicians have determined that the drug is a generalized inhibitor which means it causes certain chemicals like cAMP and cGMP to increase. Thus, the higher the levels of cAMP the greater the ability to smell. This is true to a lesser extent for cGMP. It had been used widely in the l940s and 1950s for the treatment of asthma and has been shown to restore the biochemical problems associated with smell loss in recent years. It has not, however, been approved by the FDA for this purpose.

Results

At the end of the study the researchers found that:

• Psychophysical measurements showed that smell function had increased for more than 70 percent of the participants.
• Subjective measurements showed an increase in smelling ability for 47 percent of the participants.
• No correlation in theophylline blood levels changes were evident between those whose smell loss improved and those whose smell level did not improve.
• There were no significant differences in improvement based on gender or age.
• When patients improved and stayed on the drug they continued to improve. Conversely, if they improved their ability to smell then stopped the drug they lost the gains they had made in their ability to smell.

Conclusion

According to Dr. Henkin, "It is well known that millions of Americans have smell loss. It is less well known that many of these patients have lower than normal levels of cAMP and cGMP and that theophylline is useful to them since it increases the proteins in the mucus levels of their nasal passages." He continued, "These findings do not relate to all patients with smell loss but to the many who have this biochemical abnormality. In a similar vein, treatment of patients with high cholesterol with cholesterol lowering agents is useful in treatment of heart disease, but there are many causes of heart disease besides elevated cholesterol."

A screening test for those with biochemistry-based smell loss is at: http://www.tasteandsmell.com/.

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Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society has been an integral part of this discovery process since it was established in 1887.

The APS annual meeting is part of the Experimental Biology 2008 (EB '08) gathering and runs April 5-9, 2008 at the San Diego, CA Convention Center.

Source: Donna Krupa
American Physiological Society

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