The treatment led by the University of Michigan uses gene therapy to regrow cilia, cell structures that are essential for olfactory function.
"These results could lead to one of the first therapeutic options for treating people with congenital anosmia," James F Battey, director of National Institute on Deafness and Other Communication Disorders, said.
"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," Battey said in a statement.
Olfactory dysfunction can be a symptom of a class of genetic disorders, known as ciliopathies, which include diseases as diverse as polycystic kidney disease and retinitis pigmentosa, an inherited, degenerative eye disease that causes severe vision impairment and blindness.
The disorders are caused by defects in cilia, antenna-like projections on cells that help them sense their environment.
Scientists believe that nearly every cell in the body has the capacity to grow one or more cilia.
In the olfactory system, multiple cilia project from olfactory sensory neurons, sensory cells that are found in the olfactory epithelium, tissue high up in the nasal cavity.
Receptors that bind odorants are localised on the cilia, which is why a loss of cilia results in a loss in the ability to smell.
The researchers worked with a mouse model carrying a mutation in the IFT88 gene.
The mutation causes a decrease in the IFT88 protein, which leads to a dramatic reduction in cilia function in several different organ systems, including the olfactory system.
The study used an adenovirus to introduce a healthy copy of the gene as a way to restore IFT88 protein levels in the mice.
They wanted to see if the reintroduction of the lost protein could restore cilia to the olfactory sensory neurons and return the ability to smell.
For three consecutive days, the mice received intranasal gene delivery therapy and then were allowed 10 days for the infected sensory neurons to express the viral-encoded IFT88 protein. After that time, the mice were tested with increasing concentrations of an odorant (amyl acetate).
Their responses were measured at the cellular, tissue, and synaptic levels, which all indicated that the mice had regained olfactory function.
The study was published in the journal Nature Medicine.
