New Therapies for People Who Have Lost Their Sense of Smell

Neuroscientists discovered a genetic trigger that makes the nose renew its smell sensors, new therapies for people who have lost their sense of smell due to trauma or old age.

Neuroscientists from the University of California, Berkeley, have discovered a genetic trigger that makes the nose renew its smell sensors, promising new therapies for people who have lost their sense of smell due to trauma or old age.

The gene tells olfactory stem cells the adult tissue stem cells in the nose to mature into the sensory neurons that detect odors and relay that information to the brain.

Anosmia | Loss Of Smell - Causes Symptoms Signs Diagnosis Treatment
Anosmia is the inability to perceive smell. Most patients with anosmia complain of losing the sense of taste (ageusia) and of not enjoying food.

"Anosmia the absence of smell is a vastly underappreciated public health problem in our aging population. Many people lose the will to eat, which can lead to malnutrition, because the ability to taste depends on our sense of smell, which often declines with age," said lead researcher and campus neuroscientist John Ngai.

"One reason may be that as a person ages, the olfactory stem cells age and are less able to replace mature cells, or maybe they are just depleted," he said. "So, if we had a way to promote active stem cell self-renewal, we might be better able to replace these lost cells and maintain sensory function."

Gary K. Beauchamp, director of the Monell Chemical Senses Center in Philadelphia, who was not a member of the research team, noted that the olfactory system stands out for its ability to regenerate following injury or certain diseases

Sinusitis - Types, Causes, Symptoms, Diagnosis, Complications and Treatment
Infections like sinus headache and stuffy nose can be due to acute or chronic sinusitis, affecting the maxillary sinus and other sinuses.

"This new paper … presents an elegant analysis of some of the underlying genetic mechanisms regulating this regeneration," Beauchamp said. "It also provides important insights that should eventually allow clinicians to enhance regeneration, induce it in cases where, for currently unknown reasons, olfactory loss appears permanent, or even prevent functional loss as a person ages."

The discovery may also help scientists harness olfactory stem cells and stem cells found in other sensory systems more generally, to recover sensory function following injury or degenerative disease, said Ngai, the Coates Family Professor of Neuroscience in UC Berkeley's Department of Molecular and Cell Biology and director of the Helen Wills Neuroscience Institute and the QB3 Functional Genomics Laboratory.

Accident and Trauma Care - Golden Hour - Taking Care - Don’t
Accident and trauma care is an important public health challenge that requires immediate attention. Injury (trauma) is the leading cause of death for all age groups under the age of 44.

Ngai, post-doctoral fellow Russell B. Fletcher and their UC Berkeley colleagues report their findings in the Dec. 8 issue of the journal Neuron.

Self-renewal or differentiation

Advertisement

Post Traumatic Stress Disorder (PTSD) - Causes, Symptoms, Risk Factors, Complications, Dignosis, Treatment
Post Traumatic Stress Disorder (PTSD), is a mental condition triggered by a traumatic event. PTSD treatment includes pyschotherapy, behavior therapy and medications.
In the nose, smell sensory neurons live only about 30 days, then are replaced by new cells. The new cells are generated by adult stem cells in the olfactory epithelium. A key question, Ngai said, is what tells the stem cells to divide into new ones a process called self-renewal or to mature, or differentiate, into fully functional sensory nerve cells and other cells critical to maintaining olfactory function.

"These stem cells are capable of reconstituting the entire sensory epithelium of the nose following injury," Ngai said, "so understanding how these stem cells work is important for understanding the regeneration process that goes on in the nose."

Fletcher and Ngai screened nose epithelial cells for regulatory genes and discovered one, called p63, that was a previously known transcription factor that acts by controlling the transcription of other regulatory genes in epithelial stem cells, such as those in the skin, the lining of the airways and the prostate. By knocking out the p63 gene in mice, they showed that nasal olfactory stem cells rapidly differentiated into sensory neurons at the expense of the stem cells themselves.

"This gene produces a molecule that is like a brake on the stem cell," Fletcher said. "When the brake is on, stem cells self-renew. If you remove the brake, the stem cells go into differentiation."

A drug that regulates p63, or modulates one of the genes that p63, in turn, regulates, might be able to boost the number of nasal stem cells as well as the number that mature into smell neurons.

Because p63 is found in many epithelial tissues, Ngai noted, these findings could be applied to other adult tissue stem cells including stem cells in the skin and possibly lead to future therapeutic "cell replacement" strategies to take the place of damaged or dead cells not only in the nervous system but in other epihelial tissues in the body.

Source-Eurekalert