Smelling For The First Time

Main Category: Genetics
Also Included In: Ear, Nose and Throat;  Biology / Biochemistry
Article Date: 05 May 2007 - 6:00 PDT

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New discoveries about the biochemical basis of the majority of cases of the congenital inability to smell any odor, no matter how strong, have enabled their discoverer, Dr. Robert I. Henkin, director of The Taste and Smell Clinic in Washington, DC, to treat such patients, enabling them to smell something for the first time in their lives.

These patients respond with amazement, Dr. Henkin told fellow scientists gathered at Experimental Biology 2007 meeting in Washington. "Until the treatment began to take effect, they had never experienced the olfactory world that surrounds us all, and it is with excitement that they quickly begin to learn what different things smell like and to relate those odors to objects they have known all their lives," says Dr. Henkin.

Dr. Henkin's Experimental Biology presentation was part of the scientific program of The American Physiological Society. His study is the first to characterize the biochemical abnormalities in these patients and the first to successfully treat patients using this new understanding.

In the United States alone, there are about 400,000 people who have never smelled anything in their lives. (This does not include those who lose their once normal smell function because of illness or accident.) A relatively small percentage - 12 percent - of individuals with congenital smell loss have multiple anatomical abnormalities of the brain and other organs. The vast majority - 88 percent - of individuals with congenital smell loss, however, do not have any such obvious organ abnormalities and their olfactory nerves and the brain regions that process olfactory information are intact.

Why, then, have they never been able to smell?

In order to answer that question, Dr. Henkin examined these seemingly normal patients' nasal mucus, the fluid that bathes the olfactory nerve receptors. From earlier studies in his laboratory, Dr. Henkin knew that the nasal mucus contains growth factors responsible for olfactory stem cell maturation and function. Without these growth factors, olfactory receptor cells can not maintain normal cell function. As he suspected, the nasal mucus from these patients was deficient in these important growth factors.

The studies also found a double whammy in these patients' nasal mucus. Normal mucus contains not only growth factors to allow new olfactory receptor cells to function, it also contains death factors that kill the aging receptor cells (a normal process of programmed cell death, or apoptosis), making way for the new. The congenital smell loss patients had five to 10 times the concentration of these death factors as do people who can smell. That guaranteed that the high concentration of death factor would destroy any receptor cell growth that was able to take place.

After determining the family of enzymes to which the growth and death factors belong and defining the biochemical pathway responsible for these factors, Dr. Henkin was able to treat these patients with PDE inhibitors that increase the concentration of growth factors and inhibit the secretion o death factors in nasal mucus. The treatment has been successful in restoring smell function in some of these patients, with the higher the dose and longer the use having the greatest effect.

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Contact: Sylvia Wrobel
Federation of American Societies for Experimental Biology

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