A team of scientists hasrestored the sense of smell in mice with a human genetic disorder causing congenital anosmia, that is, the innate inability to perceive odors. The new treatment uses gene therapy to get theeyelashessential cellular components for olfactory function, can grow. These hair-like structures are implicated in multiple diseases, as the authors explain in the journalNature Medicine.
Olfactory dysfunction can be one of the symptoms of a class of genetic disorders known asciliopatías, which include diseases as diverse as polycystic kidney disease and retinitis pigmentosa, an inherited eye disease that causes severe vision impairment and blindness.
The disorders are caused bycilia defects, “hairy” projections of cellsthat help them perceive their surroundings. Scientists believe that almost every cell in the body has the ability to produce one or more cilia. In the olfactory system, multiple cilia project from olfactory sensory neurons, the sensory cells found in the olfactory epithelium, high up in the nasal cavity.Receptors that bind to odorants are located in the cilia, so a loss of them eliminates the ability to smell.
The team of researchers, led by Jeffrey R. Martens of the University of Michigan, used an adenovirus to introduce a healthy copy of the gene that causes anosmia into mice, affectingIFT88 protein levels. In this way they wanted to find out if the reintroduction of the lost proteins could restore the cilia of the olfactory and sensory neurons.return the ability to smell.
For three consecutive days, the mice received intranasal gene delivery therapy and then rested 10 days for the infected sensory neurons to express the virus-encoded IFT88 protein. After this time, the olfactory capacity of the mice was tested with increasing concentrations of an odorant, amyl acetate. The responses, measured in cell tissue and synaptic levels, indicated that all mice had regained olfactory function. “By restoring protein in olfactory neurons, we endow the cell with the ability to develop and expand dendrite cilia, that is, what the olfactory neuron needs to detect odors,” explains McIntyre.
The change in olfactory function also hadimplications in the feeding behavior of mice. The mouse model used by the scientists was born underweight, and its anosmia interfered with motivation to eat, which in many mammals, including humans, is driven by smell. Treatment with adenovirus therapy increased body weight by 60 percent in the treated mice, indicating that restored olfactory function motivated feeding.
