When Dr. Kourosh Parham conceived a first-of-its-kind blood test for tinnitus, he knew further research was needed to confirm a link between a unique ear protein and the common hearing disorder. To validate his theory, the professor of surgery at UConn Health (UCH), Division of Otolaryngology-Head & Neck Surgery, teamed up with fellow UCH physician-scientists to conduct two clinical trials.
Five years later, the findings of their studies, published in March and July in the journals Otology & Neurotology, and Otolaryngology – Head & Neck Surgery, respectively, offer the strongest evidence yet that the protein, called prestin, may play a role in tinnitus. Parham hopes the breakthrough will spark larger studies and the development of a drug to treat the condition.
In both studies, Parham and fellow researchers Dr. Daniel Roberts, a neurotologist in the Department of Surgery’s Division of Otolaryngology – Head & Neck Surgery; and Dr. Erika Skoe, a hearing scientist in the Department of Speech, Language and Hearing Sciences, found elevated levels of prestin in individuals with tinnitus. Prestin enables outer hair cell (OHC) function in the cochlea, the snail-shaped organ in the inner ear. OHC are specialized cells that amplify sound vibrations in the inner ear and fine tune hearing sensitivity.
“We now have proof-of-concept that an ear protein may play a central role in the development and management of tinnitus,” says Parham. “Our work now says there is promise in using prestin as a biomarker for tinnitus. This is our first step to developing drugs to help manage tinnitus.”
While hearing loss can be inherited, it is most often acquired through acoustic trauma, prolonged exposure to loud noise, or toxicity from medications such as chemotherapy, which can lead to damage of the intricate cellular components of the inner ear.
Tinnitus is a common condition associated with hearing loss. It is characterized by a persistent, unexplained ringing, buzzing, or banging in one or both ears, heard only by the person experiencing it. It affects approximately 11% of Americans and 15% of the global population. At its worst, the condition can have a significant impact on quality of life, from sleep disturbances and cognitive dysfunction to anxiety and depression.
When Parham began researching inner ear problems about 40 years ago, tinnitus was an enigma. It was while exploring biomarkers for vertigo, and later prestin as a biomarker for noise-induced hearing loss and certain cancer drugs, that he became aware of an experimental study of aspirin toxicity commonly associated with tinnitus that pointed to prestin being a factor in the hearing disorder. Prestin sits inside the wall of the outer hair cell, which becomes longer or shorter based on the intensity of sound.
Parham speculated that some of the prestin spills into circulation under certain conditions, reflecting what is happening at the outer hair cell level. His now-patented blood test not only detects the inner ear damage at an earlier stage, but it also helps inform clinicians about the extent of the hearing loss by measuring the level of prestin in the blood.
When it comes to tinnitus, prestin may be the first objective assessment of what had previously been a subjective problem, Parham says. Prior to the test, doctors had to rely on reports from patients about the severity of their tinnitus based on assessments of how well they slept or how much stress they were feeling because of the tinnitus.
“Now, measuring prestin gives us a clinical indication of how bad the tinnitus is,” he says.
Last year, Parham’s research on prestin was highlighted in Tinnitus Today, a publication of the American Tinnitus Association. His investigation of serum prestin as a biomarker for tinnitus was funded by a Donald Bowman Innovation in Tinnitus Research Grant Award from the association.
The findings of the two recent studies are based on a small number of participants. The one published in March measured levels of prestin in 89 subjects, 49 with chronic tinnitus, and 40 control subjects. The study published in July looked at levels of prestin and other proteins in 82 participants, 41 of which reported chronic noise in both ears, and 41 control subjects.
While it’s tempting to jump to conclusions, Parham is urging caution at this stage. The results need to be replicated and confirmed in a larger sample of subjects. But replication and extension of the findings could firmly position serum prestin as a biological indicator for tinnitus.
“Having a biomarker for tinnitus is potentially a gamechanger,” the March study notes. “Availability of a biomarker for tinnitus would offer a novel tool in future investigations that may position investigators to successfully gain insights into the mechanisms that contribute to the generation of tinnitus and identify specific targets for interventions.”
