Mice regain sense of smell after gene therapy
Gene therapy can restore sense of smell in mice by correcting malformed hair-like sensors in their nose. The study suggests that abnormalities in these structures, called cilia, can be treated, and that the technology may also be applicable to other disorders, such as blindness and kidney disease.
The researchers were working with mice with a mutation that has similar effects to polycystic kidney disease in people. The mutation in the gene affects the protein that it encodes, called intraflagellar transport 88 (IFT88). The faulty protein disrupts formation and function of sensory structures called cilia on the surface of a number of different cell types across the body, not just in the nose. This causes impaired growth, extra digits, blindness and brain abnormalities.
Suspecting that the faulty cilia would affect smell, the researchers examined the neurons in the noses of the ORPK mice. In healthy mice, numerous cilia project from the nerves to capture smells in the nose, but ORPK mice had fewer cilia, and those that remained were shortened and malformed. As expected, these mice also had a deficient sense of smell.
To reverse this defect, the researchers inserted a gene encoding a functional IFT88 protein into a harmless virus and then injected the virus into the noses of mice. The virus swapped the faulty gene for the functional copy. This restored normal cilia number and structure as well as sense of smell.
The injection only affected cells in the nose. If the gene therapy is modified to target other tissues then it may be used to correct the cilia defects in other parts of the body. Faulty cilia are associated with diseases of the brain, eyes and kidneys.