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Making Sense of Lost Scent

Losing one’s sense of smell isn’t just an inconvenience, says rhinologist and researcher Andrew Lane; it also takes away some of the zest and comfort of life. There are no more good smells. Eating isn’t as pleasurable. There’s also no early warning when there’s a fire or gas leak, or when food goes bad.
“It’s a huge quality of life issue,” Lane says, and one that’s suffered by countless people with chronic sinusitis, a condition he treats frequently in his patients. As the sinus passages become inflamed, even though air still reaches the olfactory lining, patients often lose the ability to smell either temporarily or permanently.
Driven by an obligation to these patients, Lane and colleagues at his Johns Hopkins lab are working to better understand exactly what causes loss of smell in sinusitis and, eventually, to find a cure. Using mouse models—a good proxy for humans, since they share similar olfactory tissues—the researchers have performed several studies over the past few years that have each lent separate clues.
By inducing inflammation in the nasal passages of these animals, akin to what happens in chronic sinusitis, the researchers found that within a couple of weeks, tests to measure the electrical activity of olfactory tissues showed that the ability to sense scents had significantly decreased. Though the smell-sensing nerve cells were still alive at that point, further experiments showed that with bouts of inflammation just a few weeks longer, these cells quickly died off.
Unlike the vast majority of nerve cells, olfactory neurons have the capacity to regenerate—an important quality for long-term survival when so many die off after colds and other normal wear and tear. Lane and his colleagues have found in the early stages of inflammation, the progenitor cells that produce olfactory neurons seem to be trying to replace those that are dying off, but they get “stuck,” never progressing past a few cell divisions. If inflammation subsides, within weeks these neurons repopulate as if nothing had ever happened. But if this cycle happens again and again, or if inflammation is very prolonged, Lane says, they may lose the ability to regenerate forever.
Though such experiments would be impossible to perform in people, due both to the difficulty in reaching the human olfactory neurons and the inability and ethical problems of manipulating inflammation, Lane’s lab has some evidence that a similar phenomenon happens in his patients. Tissue biopsies have suggested the same lack of progression in olfactory neuron progenitor cells for patients who haven’t had sinusitis long, as well as wholesale olfactory neuron die-offs in patients who have suffered for years.
Though he’s not yet developed a cure that could help maintain these neurons when the olfactory system is inflamed, Lane says that these findings get him and other researchers closer to the right direction.
“The patients I treat, the problems they have and the frustration of sometimes not having anything to offer them motivates everything I do in the lab,” Lane says. “Patients with olfactory loss frequently ask me, ‘Why do I have this?’ and unfortunately the current answer is that no one really knows. Through my research, I’m trying to understand their disease better so that, eventually, I can give them back their sense of smell.”
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