Michigan tops STAT Madness voting with a potential treatment for tinnitus

It all came down to two tantalizing discoveries. One, from the University of Michigan, promises a potential treatment for the phantom noises that plague people with tinnitus, grounded in basic science tested in guinea pigs. Another, from the University of Utah, plumbs the genomes of wildly different animals for genes with human counterparts that might offer opportunities for cancer resistance, better metabolism, or longevity.

These were two of a record 160 inventions or discoveries entered into STAT Madness, a competition for scientific superstardom modeled on college basketball’s March contests to pick a men’s and women’s national champion. STAT editors whittled down the entries to 64 contenders for bracket-style voting by the public.  

Now the people have spoken: The popular winner is Michigan Medicine’s experimental device for treating tinnitus. In the final round, it prevailed over University of Utah Health — with 65 percent of the vote. 

Michigan’s triumph didn’t come without drama: It first had to survive a recount of sorts in the previous round. After spotting an irregular voting pattern in the final minutes of the semifinal round last week, STAT rejected a large number of votes that were cast in violation of STAT Madness rules. That resulted in Michigan Medicine prevailing over Baylor College of Medicine. STAT’s inquiry found no evidence that Baylor had anything to do with the improper votes.

For two decades, Susan Shore, a professor in Michigan Medicine’s department of otolaryngology-head and neck surgery, has been studying how different cells in the brain’s auditory system process sounds, including how these cells interact and what happens to that circuitry after noise damages the part of the brain that gets input from the ear. About 15% of Americans experience some form of tinnitus, sometimes called ringing in the ears, and it’s disabling for about 2 million people.

Shore began testing a model of tinnitus in guinea pigs to see what goes wrong. In normal hearing, neurons that fire in response to sound synchronize with other, touch-sensitive neurons in the face and neck. Specialized cells code the information from both sensory systems together, helping localize sounds when the head or face moves, for example.

But in tinnitus, neurons are hyperactive, firing spontaneously and synchronizing with each other when there is no sound to be heard. That information is conveyed to higher centers in the brain, where perception occurs.

Shore and her team learned that how auditory and touch-sensitive stimulation are paired is important. They figured out how to combine the two sensory systems in such a way that they could change how neurons fired, and in the process turn tinnitus down. In the guinea pigs, when sounds and weak electrical pulses were alternated, these cells fired less, changing both how the animals behaved and how particular signals fired in the animals’ brains — both signs of reduced tinnitus.

Next, they tested the device in two groups of 10 people with tinnitus. In one group, the device generated a sound akin to their phantom noise as well as a mild electrical pulse to the face or neck for 30 minutes a day for four weeks. The other group received a sham treatment. After a four-week break, the 10 people in each group then switched from real to sham or sham to real treatment.

Those who received the electrical stimulation said their tinnitus was reduced, lessening with each week the trial went on. Their psychological distress was relieved for even longer, after the trial was over.

“The exciting part of this work is that whatever we did in the human was taken from very solid, rigorous basic science work in animals,” Shore said about her team’s 2018 paper in Science Translational Medicine. “I think that is a big strength because not many treatments for tinnitus are actually developed directly out of the basic science by the same researcher.”

Another larger clinical trial will yield results next year, Shore said. She holds a patent on the device. “It’s always hard to predict how long commercialization can take, but I would say if we get as encouraging results in the next trial that we will work very hard to get this to people.”

If guinea pigs were important to tinnitus research, elephants, bats, ground squirrels, orcas, dolphins, and naked mole rats were the focus of University of Utah researchers puzzling out the rapid evolution of some remarkable traits in mammals with biomedical relevance to humans.

The elephant, for example, is huge. That kind of size requires extraordinary amounts of cell divisions, which invite the accumulation of genetic mutations. But elephants have extremely low rates of cancer, owing to powerful genes that regulate DNA repair that are clustered in the same genomic region where this “superpower” rapidly evolved.

In the same way, hibernating 13-lined ground squirrels offer lessons in how their bodies recover from insulin resistance, obesity, and other metabolic problems once they emerge in spring from their wintertime torpor.

Targeting those genes, which don’t encode proteins but orchestrate how other genes act, could be helpful in engineering treatments in people, the scientists believe.

“I think learning how the noncoding part of the genome works is going to change how we think about disease risk, opportunities for therapeutic intervention, and coming up with better preclinical strategies,” said Christopher Gregg, assistant professor of neurobiology and anatomy at the University of Utah. “It’s a hard problem, but comparing genomes between different species can help reveal the important elements in how it works.”

Elliott Ferris, first author of the 2018 Cell Reports paper about these animals and their superpowers, put it more simply.

“We’re interested in cancer resistance or longevity or insulin resistance,” he said. “Nature has already performed the experiments.”