Scientists restore sense of smell to mice who were born with genetic abnormality
Posted: September 4, 2012 at 7:12 am
(CBS News) There may be hope for people who are unable to smell. Using gene therapy, scientists have successfully restored the sense of smell in mice that had a genetic mutation that took away their olfactory senses.
Smell disorders or olfactory dysfunction affect one to two percent of people living in North America, according to the National Institute of Deafness and Other Communication Disorders (NIDCD). They partially funded the study along with the National Institute on Diabetes and Digestive and Kidney Diseases (NIDDK), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Eye Institute (NEI).
However, smell problems increase with age. A study showed that about 25 percent of men between the ages of 60 to 69 and 11 percent of women in that age group had developed a problem with their sense of smell, NIDCD said.
Scientist hypothesize that olfactory dysfunction may be due to a group of genetic disorders called ciliopathies, which include diseases such as polycystic kidney disease and retinitis pigmentosa, an inherited degenerative eye disease that causes severe vision impairment and blindness. Problems with cilia, antenna-like projections on cells that help sense what's around, are the root of these distorders. The cilia are found on olfactory sensory neurons where are located in tissue high up in the nasal cavity in the olfactory system.
In order to see if they could reintroduce the sense of smell, researchers from the University of Michigan tested mice that had a mutated version of the IFT88 gene. When working normally, the gene creates the IFT88 protein which is necessary for the in the development of cilia. Without it, cilia function decreases especially in the olfactory system. The same genetic problem in humans causes congenital anosmia, the inability to smell from birth.
They injected the subjects with an adenovirus - in this case, a version of the common cold virus - with the missing normal IFT88 sequence. Theoretically, it would "infect" the mice's DNA and insert the correct gene into the cells. The mice were given the therapy for three days via the nose and then given 10 days to allow the IFT88 protein to grow.
Two weeks after the three-day treatment, the mice had gained 60 percent of their body weight meaning they were eating more. Often, mice missing the protein are underweight because their lack of smell gives them less motivation to eat. Other tests showed that the neurons connected to smell were working correctly when the mice were exposed to amyl acetate, a strong-smelling chemical also called banana oil.
"Using gene therapy in a mouse model of cilia dysfunction, we were able to rescue and restore olfactory function, or sense of smell," says senior author Jeffrey Martens, an associate professor of pharmacology at University of Michigan, said in a press release. "Essentially, we induced the neurons that transmit the sense of smell to regrow the cilia they'd lost."
The authors said they hope to continue their research on mice who are completely lacking the IFT88 protein and see if there is a way to use the therapy to restore the sense of smell to people who were born with anosmia.
"These results could lead to one of the first therapeutic options for treating people with congenital anosmia," Dr. James F. Battey, Jr., director of the National Institute on Deafness and Other Communications Disorders (NIDCD), said in a press release. "They also set the stage for therapeutic approaches to treating diseases that involve cilia dysfunction in other organ systems, many of which can be fatal if left untreated."
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Scientists restore sense of smell to mice who were born with genetic abnormality
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