The Role of Biotechnology in Audiology: An Interview with Dr. Mark Parker





Author: Brian Taylor, Au.D.

While many audiologists are busy conducting their workaday routine of conducting hearing assessments, case histories and hearing aid consultations, we are reminded in this interview with Dr. Mark Parker, director of audiology, Steward St. Elizabeth's Medical Center and assistant professor of Otolaryngology at the Tufts University School of Medicine there is a leading edge of clinically oriented, research audiologists actively participating in hair cell regeneration and other futuristic biotechnology endeavors. Anyone interested in how biotechnology might change how future audiologists spend their time the clinic will be fascinated by some of the emerging trends highlighted by Dr. Parker.

AP: Dr. Parker, tell us about your background and how you became interested in biotechnology as it applies to the treatment for sensorineural hearing loss.

MP: Well, my paternal grandparents are deaf, my father is a successful private practice audiologist in Los Angeles, which is a family affair that also employs my brother as the acting director and my sister as a practicing audiologist. My maternal grandfather was also hearing instrument specialist. Growing up in my family, we spoke of (or more often signed) audiology at virtually every meal.

When I was taking my intro to audiology classes as an undergraduate at San Diego State University, we discussed Corwin & Cotanche’s (1998) seminal paper describing hair cell regeneration in chicks. The implications of that finding floored me; that if we could find the mechanisms of hair cell regeneration in birds, and then apply that to humans suffering from hearing loss, then perhaps we could build a better hearing aid using biological tools.

On the advice of my college advisor, I started taking basic science classes (chemistry, biology, physics) in addition to my audiology classes, so that I could understand the science behind hair cell regeneration. I continued taking science classes (biochemistry, genetics, cell biology) alongside my MS graduate work in speech and hearing sciences (audiology) at Portland State University. After this, I thought about pursuing an Au.D., but at that time Baylor was the only program accepting students for this new degree. I found my heart was pulling me towards research, so I decided to pursue a Ph.D. in Neuroscience. After completing my Ph.D. at Louisiana State University Health Sciences Center in New Orleans, I was lucky enough to be accepted in Douglas Cotanche’s laboratory at Boston Children’s Hospital and Harvard Medical School to conduct my post-doctoral research fellowship in hair cell regeneration. Here, we were the first group in the United States to inject stem cells into the cochleas of sound-deafened mice and guinea pigs.

AP: Over the past decade or so, there have been reports of biomedical approaches to restore or repair auditory organs. Can you summarize what these reports say?

MP: The best summary I can think of is that it is very hard to make a chicken deaf, but very easy to make a mouse deaf. More specifically, almost all animals, with the exception of mammals (humans, monkeys, mice, etc.), maintain the capacity for spontaneous regeneration of their auditory organs, including hair cells, supporting cells, and neurons. If you create a loud noise or give an ototoxic dose of gentamicin to a chicken, its cochleas will become damaged similar to ours, but its peripheral auditory stems will spontaneously repair themselves and functional hearing will be restored. Unfortunately, our understandings of the precise mechanisms responsible for systemic auditory regeneration are incomplete.

As we all know from our clinical practice, mammals do not possess the capacity of spontaneous regeneration of their auditory systems. However, there have been great strides made in terms of hair cell regeneration and regeneration of the spiral ganglion neurons that connect the hair cells to the brain. For instance, both gene therapies and drug therapies have been shown to induce hair cell regeneration in several mammalian animal models. Also, cell-based therapies have shown some promise in restoring lost spiral ganglion neurons in mammalian noise damaged and auditory neuropathy animal models.

AP: What is the basic science behind hair cell generation? How does it work?

MP: There is a gene called atonal homolog-1 (Atoh1), that when is turned on (expressed) in cochlear supporting cells, causes the supporting cells to develop into a hair cells. There are several drugs and gene therapies that act to express Atoh1 in the damaged cochlea to drive the remaining supporting cells to replace dead or damaged hair cells.

AP: Besides hair cell regeneration, are there any other biomedical approaches that may be applied to audiology?

MP: Yes, in addition to the stem cell-based therapies being used to replace damaged spiral ganglion neurons, there are other drug and gene therapies aimed to promote spiral ganglion survival to help cochlear implant patients. There is also a gene therapy aimed to repair the defective connexin 26 gene, which is the leading cause of non-syndromic sensorineural hearing loss in humans.

AP: How might gene therapy be used in the clinic?

MP: Novartis has initiated clinical trials using the Atoh1 gene to induce hair cell replacement. In this system, a virus is used to transfer the Atoh1 gene into to cochleas of hearing impaired patients. In the future, I can see an ENT surgeon infecting a hearing impaired person with an inactive form of Atoh1, and then prescribing the person an oral drug to induce Atoh1 expression and hair cell replacement.

AP: I know you don’t have a crystal ball, but how do you see further generations of audiologists using hair cell regeneration techniques clinically and what role will audiology play?

MP: I view this similarly to our division of labor regarding cochlear implants. I don’t foresee audiologists injecting stem cells or genes into the cochleas of humans anytime in the near future. I believe that ENTs will remain the experts here. However, I do see a growing opportunity in terms of audiologists developing and conducting better functional measurements of the auditory system.

Quite frankly, our current methods (i.e. obtaining an audiogram) are crude assessments of the auditory system because we cannot determine whether the hearing loss is due to hair cell or spiral ganglion damage. They both present the same on an audiogram. This is important in terms of biological treatments because we need more precise tests to determine whether a hearing loss is due to hair cell damage, which would lead to Atoh1 gene therapies for hair cell replacement, or due to spiral ganglion degeneration, which could lead to cell-based therapies for spiral ganglion replacement. Measuring hidden hearing loss and dead regions of the cochlea are hot topics of auditory research and are leading to better tests to assess of the integrity of inner hair cells, outer hair cells, and spiral ganglion cells. So, to answer your question, I see the growing role of audiologists as the experts in diagnosing the otopathology of sensorineural hearing loss and measuring the effectiveness of these future treatments.

AP: Hair cell regeneration may be in its infancy, but it sounds like it has a future. What resources are available today to help the clinical audiologist better understand biotechnical approaches to the treatment of sensorineural hearing loss?

MP: I have published a summary of this field that was written for the clinical audiologist who is interested in the topic of hair cell regeneration, but who is not trained in the science underlying these studies (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163053/). Hopefully this paper will help the interested clinician fill in the gaps between her training and the type of scientific training required to better comprehend the science behind the primary sources. I have also recorded a webinar on the AAA website where you can learn about this topic in greater detail.    
Mark A Parker Ph.D., CCC-A is Director of Audiology at Steward St. Elizabeth’s Medical Center and Assistant Professor of Otolaryngology at Tufts University School of Medicine. You can read more about Dr. Parker and his work at www.researchgate. net/profile/Mark_Parker5.