VCU news

By Leah Small

Scott Moorehead was thrown into a deep depression when he lost his sense of smell five years ago due to a traumatic brain injury. Moorehead fell in the driveway of his Marion, Indiana, home while teaching his then 6-year-old son, Mason, how to skateboard.

Moorehead suffered a major concussion and internal bleeding, but the long-lasting consequence was severing the connection of the olfactory nerves in his nose to his brain, which resulted in total smell loss, or anosmia.

It is an “invisible injury,” Moorehead said. The sense’s tie to memory and enjoyment made the loss debilitating.

“Until you can’t smell at all you have no idea how emotional the experience can be,” he said. “You start to think about these really awful things, like, someday my daughter is going to get married and I’m going to walk her down the aisle and I’m going to give her a big hug, and I’m going to have no idea what she smelled like.”

Moorehead is one of the roughly 6.3 million people nationally who have reported a loss of smell, according to the Monell Chemical Senses Center. Many of these people report feeling socially isolated and in danger because they cannot detect hazards such as gas leaks and spoiled food. They frequently don’t enjoy eating and drinking, because taste is tied to smell, and feel less confident of hygiene. Smell loss has been linked to depression and difficulty forming memories. This may be because smells are closely tied to the brain’s limbic system, which has key functions for stimulation, emotion and memories. Smell loss is often connected to head trauma, viral infections and diseases associated with aging.

Desperate for relief, Moorehead searched for solutions for his condition but was told by multiple specialists that nothing could be done. Three years later, after he said he stopped looking for a cure and “dealt with everything emotionally,” a friend told him about smell restoration technology being developed by researchers in Virginia Commonwealth University’s School of Medicine.

The news inspired Moorehead, who is CEO of The Cellular Connection, the largest Verizon retailer in the nation, to commit to funding the development and commercialization of the technology. He partnered with the inventors, VCU School of Medicine professors Richard Costanzo, Ph.D., and Daniel Coelho, M.D., and the VCU Innovation Gateway to form Lawnboy Ventures LLC, with the intent of commercializing the technology.

“I’ve been given the opportunity to live this life and I ended up with only one permanent part of my injury. My brain works, my body works, everything works and I’m extremely grateful for that,” Moorehead said. “It’s not as much about me anymore. It’s about other people who will experience the same things.”

Moorehead gave an initial round of funding this month to kick-start the commercialization efforts. Previous grants from MEDARVA Research Foundation totaling nearly $700,000 helped VCU researchers develop the technology. VCU Innovation Gateway manages the intellectual property protection and facilitates commercialization of VCU inventions. Ivelina Metcheva, Ph.D., executive director of Innovation Gateway, said the “greatest value of the VCU research enterprise is the application of discoveries.

“Transferring this invention to the private sector will enable its translation from bench to patient and will improve quality of life for many people,” she said. “This is a telling example of how our university endeavors to positively impact society.”

The offbeat name of the LLC alludes to a song released in 1990 by the rock band Phish, of which Moorehead is a fan.

“The lyrics are relevant to the mission. If you look, there’s a part [in the song] where they talk about stepping onto the lawn and smelling the olfactory hues,” he said.

 

Restoring the olfactory hues

A sensory physiologist, Costanzo, a professor in the Department of Physiology and Biophysics, has spent 40 years researching the mechanisms surrounding taste and olfaction and how to restore these senses. He works alongside physicians in VCU’s Smell and Taste Disorders Center, part of the Department of Otolaryngology. The center is one of a handful in the U.S. and throughout the world that study and provide clinical options for managing disorders of the senses smell and taste.

Costanzo receives numerous patient inquiries a year from people with anosmia. But unfortunately, there is no proven method of treating smell loss, he said.

“Unless it’s something simple such as an obstruction or growth in their nose that can be removed, such as a polyp, or a brain tumor that can be excised, there’s nothing we can do,” Costanzo said. “Most olfactory related injuries used to be due to motor vehicle accidents, now it’s people coming back from war that have blast injuries that result in anosmia.”

The brain’s ability to detect and categorize smells is a function of the central nervous system, which transmits information throughout the body via electrical impulses that travel between nerves. Olfactory receptors in the nasal cavity detect odors and send this information to the olfactory bulb, a roughly 3-millimeter region located at the bottom of the forebrain. The olfactory bulb processes odor information before it is transferred to higher functioning regions of the brain.

If the connection between the olfactory receptors and bulb is disrupted due to injury or disease, the result is smell loss.

It is a conundrum that Costanzo and Coelho, the G. Douglas Hayden Associate Professor in the Department of Otolaryngology – Head and Neck Surgery and medical director of the VCU Cochlear Implant Center, found themselves discussing over coffee in the lab nearly seven years ago. Costanzo appealed to Coelho’s surgical expertise in cochlear implants, a device that restores hearing in people with severe hearing loss.

“We noted how wonderful it is to be able to offer hearing impaired patients cochlear implants and lamented that there are not great clinical options for people with complete smell loss,” Coelho said. “Then we started talking about the electrophysiology of how cochlear implants work.”

Cochlear implants bypass damaged parts of the ear to deliver electrical signals to the auditory nerve, which then routes the signals to the brain. Coelho and Costanzo theorized they could develop a device to replace the sensory transmission and interpretation functions of the olfactory nerves. This month, the partners published an article in the journal “The International Forum of Allergy and Rhinology”  proving the concept.

“There may be a way to use some cochlear implant technology to stimulate highly selective parts of the brain that are not getting input when smell is lost and to see whether or not that could result in return of smell for patients,” Coelho said.

 

Proof of concept

In late 2016, Coelho and Costanzo received a patent for the development of an olfactory implantation device. Similar to cochlear implants, the device would use an external sensor and internal processor to detect and transmit information and stimulate applicable brain regions.

Recent prototypes show that small gas sensors will detect odor molecules and send information to a microprocessor via electrical signals. The microprocessor will then use electrical signals to direct an implanted electrode array to stimulate the olfactory bulb, producing smell.

However, fine-tuning the device to assist the brain in correctly registering all scents is an art. The implant has to be able to correctly identify gas molecules and stimulate the olfactory bulb in places that would produce the correct smell.

This requires the creation of a personalized sensory map. The physicians would stimulate the olfactory bulb of a person with anosmia in various patterns, and the patient would give feedback on what smell was produced to inform programming of the microprocessor.

“We would program the sensor input and microprocessor to know this odor is a banana and this one is a rose,” Costanzo said. “Then we match up the sensor input with a stimulation pattern for the olfactory bulb. So, if a patient goes into a room and there’s a banana smell, a specific odor pattern is activated in the bulb. Now, instead of eating mush they are now getting the banana sensation.”

The process is made somewhat less complicated by the fact that odors are not entirely distinct; they are formed by combinations of different odors.

“Although the human brain could probably smell a trillion different odorants, you probably only need 200 or so at most to really be able to identify a particular smell because smells depend on mixtures of chemicals,” Coelho said. “A rose smell is actually made up of a thousand different chemical compounds, but only a handful of those are needed to identify it is a rose.”

Success also depends on having the right number and size of microelectrodes to supply the required stimulation. This, combined with determining the patterns of electrical stimulation by those microelectrodes, was a problem posed by early cochlear implants. Some cochlear implant users could only hear a buzz. Decades later, modification of the number of electrodes and the pattern of electrode stimulation dramatically improved cochlear implants. Coelho and Costanzo think this may also be the case with olfactory implantation.

“The analogy I give is, playing the piano with one finger or hitting all of the notes at one time doesn’t sound so great,” Coelho said. “Playing with five or 10 fingers sounds great, but any more than that really doesn’t make that much of a difference to the listener.”

Costanzo, who is also developing a device that would restore the sense of taste, said such innovations are at the cusp of major advances.

“We think that much of biomedical technology in the next decade or two is going to focus on interfacing the brain with electronic devices,” he said. “We are already building portable medical devices for our phones and other things. People will have different sensors that can interface with the body to repair and replace biological systems.”