Smell Therapy: Repairing Cilia in Live Mice

A research team from Johns Hopkins and other institutions report that by restoring the tiny hair-like projections to defective cells in the olfactory system is enough to restore a lost sense of smell. The experimental results were published online in Nature magazine and, as of the publication, are believed to be the first successful application of gene therapy to restore this function in live mammals.

An olfactory expert, Randall Reed, Ph.D., professor of molecular biology and genetics and co-director of the Center for Sensory Biology at the Johns Hopkins Institute for Basic Biomedical Sciences, admonishes researchers that they are still years away from applying the same therapy in humans, and that the process will most likely only prove effective for those who have anosmia (lack of smell) as a result of genetic disorders. "But our work has already contributed to a better understanding of the cellular factors involved in anosmia, and that will give us insights into other neurological disorders, as well," he says.

The mice used in the study were all carriers of a genetic mutation that destroyed the production of a particular protein critical for the functioning of cilia in the cells responsible for smell, called olfactory sensory neurons. These specialized cells each display several of the protruding, hair-esque projections that contain receptors for odorants. Without functioning cilia, the cells act like a broken link in the chain of events necessary for proper odor detection in the environment.

Starting with a common cold virus, one which infects the cells of the nasal cavity, researchers replaced some of the viral genes with a corrected version of the defective cilia gene. They then infected smelling-impaired mice with the altered virus, delivering the corrected gene to the neural cells which needed it.

At the cellular level, researchers saw a restoration of proper chemical signaling between nerve cells after the treated mice were stimulated with various odorants. A steady indication of their success, Reed reports, was the 60 percent increase in body weight that the mice experienced once they could smell their meals, resulting in a bigger appetite. Many people who suffer from anosmia lose weight because aromas play a substantial part in creating appetite and food enjoyment.

Researchers maintain optimism about the broad implications of their work because cilia aren't only important olfactory cells, but also to cells all over the body from those in the kidneys to those in the eyes. The fact that they were able to treat live mice with a therapy that restored cilia function in one sensory system suggests that similar techniques can be applied to cilia disorders elsewhere.

"We also hope this stimulates the olfactory research community to look at anosmia caused by other factors, such as head trauma and degenerative diseases," says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at the University of Michigan. "We know a lot about how this system works – now have to look at how to fix it when it malfunctions."

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