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What if you couldn’t smell leaking gas in your kitchen, spoiled milk in your refrigerator – or the scent of your baby’s head?

The sense of smell provides a major portal on the world around us that many only come to truly appreciate once it is lost. Often described as an invisible disorder, smell loss is not uncommon. Smell disorders, including anosmia – complete loss of the sense of smell — occur in millions of people worldwide, affecting patients’ quality of life and health due to the inability to appreciate food flavor, detect environmental hazards, or fully engage with social networks and surroundings.

With 50 years of fundamental research on the mechanisms and functions of the sense of smell, the Monell Center is well positioned to make a difference for those who have lost this vital sense. Today, targeted research at the Center focuses on uncovering the basic mechanisms underlying olfactory loss and identifying treatments, with general and faculty support from the Monell Foundation contributing to the Center’s ability to carry out this important work.  

 

Identifying Treatments for Smell Loss

Causes of taste and smell dysfunction include receptor or nerve damage from viral infections such as the common cold, head trauma, cancer treatments including radiation therapy, and inborn genetic disorders. Simple aging also plays a role, and approximately one quarter of US adults age 40 and older report a problem with their sense of smell, affecting their safety, health, and well-being.

While a smell disorder can affect anyone at any time, these conditions remain under-recognized and understudied. To address this situation, the Center launched “The Monell Anosmia Project,” an anosmia awareness and research initiative, in February 2014.

A Sample of Ongoing Anosmia Research

  • Receptor Regeneration Using Stem Cells: One arm of the Center’s anosmia research explores how regenerative medicine could treat smell loss or impairment. This project takes advantage of the unique ability of olfactory receptor cells to regenerate across the lifetime. The first step involves understanding the process by which human olfactory stem cells turn into the olfactory receptor cells that sense odors.

Lead investigator Peihua Jiang, PhD, who helped identify taste stem cells on the tongue, began by focusing on mouse olfactory stem cells, which are easy to obtain and grow in cell cultures.

After many attempts, Jiang’s team identified the combination of nutrients and growth factors that prompt mouse olfactory stem cells to grow into cell clusters – or organoids — that contain mature working olfactory receptor cells.

Because of the many similarities between the mouse and human olfactory systems, Dr. Jiang expects that he also will be able to activate human olfactory stem cells to grow into working receptor cells. Using olfactory tissue from patients with a healthy sense of smell, he recently isolated human stem cells and grew them into cell clusters. The team is now analyzing these cell clusters to determine if they contain olfactory receptor cells.

The crucial next step will determine how to generate olfactory receptor cells with the same functionality as native receptor cells. After that, the team will study how to transplant the receptor cells into the noses of patients with smell disorders and guide the cells to connect with the olfactory bulb in the brain.

These studies will take several years, but Jiang and his team believe that they will one day be able to restore the sense of smell to people with damaged olfactory receptor cells caused by aging, viruses, or head trauma.

  • Identifying Genes Related to Smell Loss: Identifying genetic alterations that lead to blindness and deafness has been critically important for developing gene therapies for those sensory disorders. Scientists know of more than 100 dysfunctional genes in patients born without hearing and over 200 such genes in patients born without the sense of sight.

These numbers are in stark contrast to the number of genes implicated in patients who are born without a sense of smell, with only two such genes identified to date.

A project led by Monell Center olfactory neurobiologist Joel Mainland, PhD, is conducting genetic analyses of individuals born without smell – a condition known as congenital anosmia — and their unaffected family members. Comparing the genetic variation between anosmic and healthy family members allows Mainland and his associates to create a list of possible causal genes.

Next, genes from an additional 150 unrelated congenital anosmics will be analyzed. Any gene that is altered in multiple unrelated anosmics is likely to play a key role related to the smell loss.

When complete, this work will provide a comprehensive picture of the spectrum of genetic alterations in patients with congenital anosmia, which may improve the diagnosis, prognosis, and treatment of this disorder. In addition, the findings may lead to mechanistic insight into the causes of some types of acquired anosmia.

  • Brain and Behavior Tactics for Treating Anosmia: Just as physical therapy can help restore function to damaged muscles and connective tissue, recent clinical trials show that a simple non-invasive technique called smell training can improve the sense of smell in some people recovering from anosmia.

Cognitive neuroscientist Johan Lundström, PhD, who studies anosmic patients in both the US and Sweden, will soon begin a new study in Philadelphia to study smell training in patients with nasal polyps, who often do not show complete recovery of smell after surgery to remove the polyps.

Lundstrӧm will examine whether smell training and non-invasive stimulation of the brain — either singly or together — can enhance neural processing of smell in the brain and lead to a complete recovery of olfactory ability in these patients.

The findings will provide insight into whether smell loss is accompanied by changes in brain areas associated with olfactory processing and also into the potential of smell training to improve surgical outcome for patients with nasal polyps.

Making a Difference

“There currently are tenfold more research studies and federal research projects on the regeneration of hearing and vision than for taste and smell. The Monell Center wants to rectify this situation so we can identify fruitful therapeutic approaches to help the millions of patients with taste and smell disorders,” said Mainland.

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