Scientists have restored the sense of smell in mice through gene¹ therapy for the first time -- a hopeful sign for people who can't smell anything from birth or lose it due to disease. The achievement in curing congenital anosmia（嗅觉缺失症） -- the medical term for lifelong inability to detect odors -- may also aid research on other conditions that also stem from problems with the cilia（纤毛）. Those tiny hair-shaped structures on the surfaces of cells throughout the body are involved in many diseases, from the kidneys to the eyes.

 

The new findings, published online in Nature Medicine, come from a team at the University of Michigan Medical School and their colleagues at several other institutions.

 

The researchers caution that it will take time for their work to affect human treatment, and that it will be most important for people who have lost their sense of smell due to a genetic² disorder³, rather than those who lose it due to aging, head trauma⁴, or chronic⁵ sinus problems. But their work paves the way for a better understanding of anosmia at the cellular⁶ level.

 

"Using gene therapy in a mouse model of cilia dysfunction（功能紊乱）, we were able to rescue and restore olfactory⁷ function, or sense of smell," says senior author Jeffrey Martens, Ph.D., an associate professor of pharmacology at U-M. "Essentially⁸, we induced the neurons that transmit the sense of smell to regrow the cilia they'd lost."

 

The mice in the study all had a severe genetic defect that affected⁹ a protein called IFT88, causing a lack of cilia throughout their bodies. Such mice are prone¹⁰ to poor feeding and to early death as a result. In humans, the same genetic defect is fatal.

 

The researchers were able to insert normal IFT88 genes¹¹ into the cells of the mice by giving them a common cold virus loaded with the normal DNA¹² sequence, and allowing the virus to infect them and insert the DNA into the mouse's own cells. They then monitored cilia growth, feeding habits, and well as signals within and between the nerve cells, called neurons, that are involved in the sense of smell.

 

Only 14 days after the three-day treatment, the mice had a 60 percent increase in their body weight, an indication they were likely eating more. Cell-level indicators¹³ showed that neurons involved in smelling were firing correctly when the mice were exposed to amyl acetate, a strong-smelling chemical also called banana oil.

 

"At the molecular¹⁴ level, function that had been absent was restored," says Martens.

 

"By restoring the protein back into the olfactory neurons, we could give the cell the ability to regrow and extend cilia off the dendrite knob, which is what the olfactory neuron needs to detect odorants（有气味的东西）," says postdoctoral fellow and first author Jeremy McIntyre, Ph.D.

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