Interview with Richard D. Kopke M.D., Naval Medical Center, San Diego, California
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TOPIC: Noise Induced Hearing Loss and Possible Pharmacologic Solutions
AO/Beck: Good Morning Dr. Kopke. It is an honor to work with you this morning. I read your recent paper regarding the potential to reduce noise induced hearing loss pharmacologically - and it was very interesting. But before we get to that topic, would you please tell me a little about your professional background, if you don't mind.
Kopke: Sure Doug. I went to medical school while in the Army. I went to the University of Washington at Seattle and I finished medical school there in 1981. I did my neurotology fellowship at Albert Einstein College of Medicine in New York City. I am now a neurotologist at the Naval Medical Center in San Diego. I take care of patients with ear problems. I am a colonel in the US Army and I also co-direct the Department of Defense, Spatial Orientation Center, here at the Naval Medical Center in San Diego. We conduct hearing and balance research at the Spatial Orientation Center, with special emphasis on hearing and balance issues that might impact military personnel while executing their assignments, and on occasion we have worked with NASA on related hearing and balance issues. I also spend a lot of my time working with a team of researchers here with the goal of preventing inner ear damage from noise exposure and restoring the hearing abilities of the inner ear - after it's been damaged by noise.
AO/Beck: OK, thanks. Seems to me like we ought to explore some of these balance programs too, but today's topic is limited to prevention and management of noise induced hearing loss. So, if you would, can you please start with a thumbnail sketch of your work in this area, and an overview of how large a problem this really is?
Kopke: As you know, noise exposure is a big problem in the military, and a significant cause of hearing loss in the military, and also in industrial settings. There are estimates that in the USA and Europe some 55 million people work in hazardous noise situations. It is also estimated that ten million people in the USA have a degree of permanent noise induced hearing loss. Noise is everywhere, and it certainly causes hearing loss. Despite the use of hearing protection devices (HPDs) and despite the strides made in hearing conservation, when you look at disability payments for hearing loss and tinnitis, the cost of lost personnel, the cost of retraining personnel because the previous person had to leave their assignment due to hearing issues, and accidents related to communication errors, just the monies paid by the US military probably exceed a billion dollars a year. So it is a large problem. It is also estimated that hearing loss costs the US economy $55 billion per year. In fact, noise induced hearing loss is one of the most common disabilities in the military and the second most reported workplace injury. There are over 22 thousand hearing disability claims filed per year in the Navy, Air Force and Marines alone, not including the US Army. I used to think the military was the most significant source of noise exposure, but research indicates that some 50 percent of plumbers and carpenters, and 90 percent of coal miners have noise induced hearing loss.
AO/Beck: What about Hearing Protection Devices (HPDs) in particular, are they useful?
Kopke: Although HPDs are highly useful and I definitely endorse them, some noises are just too loud, and they exceed the ability of the HPDs to protect the ears. HPDs are better now than ever before, but they are not 100 percent effective. Their effectiveness depends on the wearer using them properly and consistently and the fit being perfect, and they can only protect the ear up to their limits, and in the military, and in some industrial settings, those loudness limits are exceeded. Another issue with HPDs is the element of surprise. By that I mean, sometimes the folks wearing the HPDs do everything right, but when they're on a break, or not wearing the HPDs, a sudden loud sound occurs, and because for that split second they were not wearing their HPDs, the loud sound gets through and the damage is done to their hearing. Additionally, it is known that when you combine certain inhaled toxins, such as carbon monoxide and perhaps jet fuel gaseous components with noise, the noise damage will indeed be greater! In fact, the noise and the inhaled fumes act as co-toxins and there is a synergistic reaction, meaning the hearing damage resulting from the two is greater than it would be for either alone in isolation. So the approach we have been taking, is to see if we can make the inner ear more resistant to both noise and toxin damage by augmenting the inner ear's defenses against this type of stress. Additionally, we'd like to enhance the inner ear's ability to repair itself, or recover from an acute noise injury, and lastly, we're working on some possible aspects of regeneration of the hair cells of the inner ear - but regeneration, is a long way down the road from where we are now. All of these projects are at this time essentially based on pharmacologic solutions, in other words, we're investigating a pill that would be useful to prevent or repair acute noise damage. And the early answer appears to be yes.
AO/Beck: Can you tell me a little bit more about the basic molecular research that supports the ongoing projects?
Kopke: Well, as you know, noise can actually be so loud that it physically tears apart the inner ear tissues. Of course, the majority of the noises humans are exposed to are loud, but not loud enough to immediately cause the damage I just described. Rather, most noise exposure causes a metabolic stress on the inner ear and then over time it leads to the generation of free radicals and reactive oxygen species from the mitochondria, and this excessive release of free radicals and reactive oxygen species exceeds the normal inner ears' ability to defend itself against those molecules. Since those molecules contain an unpaired electron, they react readily and they're volatile and toxic and they damage the cell. The hair cells and the neurons undergo cell death, such as apoptosis, and the hearing gets worse.
AO/Beck: And so your work is essentially focusing at the molecular and cellular level to see if certain chemicals can intervene in the cell death cycle?
Kopke: Yes, in essence, that is correct. One of the key inner ear issues is that free radicals and reactive oxygen species are oxidizing chemicals, and therefore if we can bolster the inner ear's anti-oxidant defenses, we can likely protect the inner ear and reduce the resultant hearing loss. By combating oxidative stress we can prevent cell death in the cochlea and avoid permanent hearing loss.
AO/Beck: I know you have to be very careful in discussing anti-oxidants because I can just imagine some people might start taking vitamins labeled anti-oxidants to try to prevent noise damage, but I'm thinking that probably isn't the answer?
Kopke: Correct. That probably isn't going to work very well. The key molecule in the inner ear that protects against this sort of damage is glutathione. Unfortunately, you cannot just give a person glutathione, and then have the glutathione level in the inner ear increase. It just doesn't work that way because the chemical is not transported very well into the cells. So what you need to do is to give the patient compounds that can be taken into the cell, and then synthesized into glutathione. We're using other compounds that are already FDA approved for other purposes, to help study and deliver the chemicals that can be utilized by the inner ear to produce glutathione. Another strategy is to work with the mitochondria to protect and restore it, and that too seems like an effective strategy.
AO/Beck: Have these experiments been done on humans, or just lab models at this time?
Kopke: Up to this point, we've studied mostly laboratory models. In fact, based on well-established model studies, the control group (untreated) winds up with about 2/3rds of their hair cells wiped out, and about a 35 to 50 dB permanent threshold shift from continuous noise or impulse noise, such as might come from an M-16 machine gun. The experimental group (treated group) with the chemical protective agents wind up with almost no hair cell loss, and almost no permanent threshold shift. So the application to humans might be that we can protect them from hearing loss based on noise exposure, and of course this would be a very significant finding. Additionally, we find that starting the chemical agents even after the noise exposure provides a benefit. Of course, as you would guess, starting the chemical before the noise exposure yields the best protection. So in essence, an oral medication is being developed based on strong basic science work, that can be taken before a loud noise exposure to prevent hearing loss, or in some cases, be taken shortly after a loud noise exposure to also reduce permanent noise-induced hearing loss. An important next step is that a pharmaceutical firm known as American BioHealth Group (ABG) is taking the lead in commercializing this technology and making it available for clinical trials.
AO/Beck: Dr. Kopke, this really is fascinating work and I applaud you for your knowledge and dedication to task. I hope we can get together again in the next 6 to 12 months to touch base and see how your work is progressing?
Kopke: Absolutely Dr. Beck. I would look forward to discussing this with you again and we'll be happy to keep you updated on our work.
AO/Beck: In the meantime, is there a website or two that you might recommend for people looking for more information about the Naval Medical Center and the work you do?
Kopke: Because American BioHealth Group is playing a pivotal roll in commercializing this pill; we suggest you visit their web site at www.ABGPharma.com. Interested parties can monitor the development process.
AO/Beck: Thanks Dr. Kopke.
Kopke: Thank you too Dr. Beck.
AO/Beck: Good Morning Dr. Kopke. It is an honor to work with you this morning. I read your recent paper regarding the potential to reduce noise induced hearing loss pharmacologically - and it was very interesting. But before we get to that topic, would you please tell me a little about your professional background, if you don't mind.
Kopke: Sure Doug. I went to medical school while in the Army. I went to the University of Washington at Seattle and I finished medical school there in 1981. I did my neurotology fellowship at Albert Einstein College of Medicine in New York City. I am now a neurotologist at the Naval Medical Center in San Diego. I take care of patients with ear problems. I am a colonel in the US Army and I also co-direct the Department of Defense, Spatial Orientation Center, here at the Naval Medical Center in San Diego. We conduct hearing and balance research at the Spatial Orientation Center, with special emphasis on hearing and balance issues that might impact military personnel while executing their assignments, and on occasion we have worked with NASA on related hearing and balance issues. I also spend a lot of my time working with a team of researchers here with the goal of preventing inner ear damage from noise exposure and restoring the hearing abilities of the inner ear - after it's been damaged by noise.
AO/Beck: OK, thanks. Seems to me like we ought to explore some of these balance programs too, but today's topic is limited to prevention and management of noise induced hearing loss. So, if you would, can you please start with a thumbnail sketch of your work in this area, and an overview of how large a problem this really is?
Kopke: As you know, noise exposure is a big problem in the military, and a significant cause of hearing loss in the military, and also in industrial settings. There are estimates that in the USA and Europe some 55 million people work in hazardous noise situations. It is also estimated that ten million people in the USA have a degree of permanent noise induced hearing loss. Noise is everywhere, and it certainly causes hearing loss. Despite the use of hearing protection devices (HPDs) and despite the strides made in hearing conservation, when you look at disability payments for hearing loss and tinnitis, the cost of lost personnel, the cost of retraining personnel because the previous person had to leave their assignment due to hearing issues, and accidents related to communication errors, just the monies paid by the US military probably exceed a billion dollars a year. So it is a large problem. It is also estimated that hearing loss costs the US economy $55 billion per year. In fact, noise induced hearing loss is one of the most common disabilities in the military and the second most reported workplace injury. There are over 22 thousand hearing disability claims filed per year in the Navy, Air Force and Marines alone, not including the US Army. I used to think the military was the most significant source of noise exposure, but research indicates that some 50 percent of plumbers and carpenters, and 90 percent of coal miners have noise induced hearing loss.
AO/Beck: What about Hearing Protection Devices (HPDs) in particular, are they useful?
Kopke: Although HPDs are highly useful and I definitely endorse them, some noises are just too loud, and they exceed the ability of the HPDs to protect the ears. HPDs are better now than ever before, but they are not 100 percent effective. Their effectiveness depends on the wearer using them properly and consistently and the fit being perfect, and they can only protect the ear up to their limits, and in the military, and in some industrial settings, those loudness limits are exceeded. Another issue with HPDs is the element of surprise. By that I mean, sometimes the folks wearing the HPDs do everything right, but when they're on a break, or not wearing the HPDs, a sudden loud sound occurs, and because for that split second they were not wearing their HPDs, the loud sound gets through and the damage is done to their hearing. Additionally, it is known that when you combine certain inhaled toxins, such as carbon monoxide and perhaps jet fuel gaseous components with noise, the noise damage will indeed be greater! In fact, the noise and the inhaled fumes act as co-toxins and there is a synergistic reaction, meaning the hearing damage resulting from the two is greater than it would be for either alone in isolation. So the approach we have been taking, is to see if we can make the inner ear more resistant to both noise and toxin damage by augmenting the inner ear's defenses against this type of stress. Additionally, we'd like to enhance the inner ear's ability to repair itself, or recover from an acute noise injury, and lastly, we're working on some possible aspects of regeneration of the hair cells of the inner ear - but regeneration, is a long way down the road from where we are now. All of these projects are at this time essentially based on pharmacologic solutions, in other words, we're investigating a pill that would be useful to prevent or repair acute noise damage. And the early answer appears to be yes.
AO/Beck: Can you tell me a little bit more about the basic molecular research that supports the ongoing projects?
Kopke: Well, as you know, noise can actually be so loud that it physically tears apart the inner ear tissues. Of course, the majority of the noises humans are exposed to are loud, but not loud enough to immediately cause the damage I just described. Rather, most noise exposure causes a metabolic stress on the inner ear and then over time it leads to the generation of free radicals and reactive oxygen species from the mitochondria, and this excessive release of free radicals and reactive oxygen species exceeds the normal inner ears' ability to defend itself against those molecules. Since those molecules contain an unpaired electron, they react readily and they're volatile and toxic and they damage the cell. The hair cells and the neurons undergo cell death, such as apoptosis, and the hearing gets worse.
AO/Beck: And so your work is essentially focusing at the molecular and cellular level to see if certain chemicals can intervene in the cell death cycle?
Kopke: Yes, in essence, that is correct. One of the key inner ear issues is that free radicals and reactive oxygen species are oxidizing chemicals, and therefore if we can bolster the inner ear's anti-oxidant defenses, we can likely protect the inner ear and reduce the resultant hearing loss. By combating oxidative stress we can prevent cell death in the cochlea and avoid permanent hearing loss.
AO/Beck: I know you have to be very careful in discussing anti-oxidants because I can just imagine some people might start taking vitamins labeled anti-oxidants to try to prevent noise damage, but I'm thinking that probably isn't the answer?
Kopke: Correct. That probably isn't going to work very well. The key molecule in the inner ear that protects against this sort of damage is glutathione. Unfortunately, you cannot just give a person glutathione, and then have the glutathione level in the inner ear increase. It just doesn't work that way because the chemical is not transported very well into the cells. So what you need to do is to give the patient compounds that can be taken into the cell, and then synthesized into glutathione. We're using other compounds that are already FDA approved for other purposes, to help study and deliver the chemicals that can be utilized by the inner ear to produce glutathione. Another strategy is to work with the mitochondria to protect and restore it, and that too seems like an effective strategy.
AO/Beck: Have these experiments been done on humans, or just lab models at this time?
Kopke: Up to this point, we've studied mostly laboratory models. In fact, based on well-established model studies, the control group (untreated) winds up with about 2/3rds of their hair cells wiped out, and about a 35 to 50 dB permanent threshold shift from continuous noise or impulse noise, such as might come from an M-16 machine gun. The experimental group (treated group) with the chemical protective agents wind up with almost no hair cell loss, and almost no permanent threshold shift. So the application to humans might be that we can protect them from hearing loss based on noise exposure, and of course this would be a very significant finding. Additionally, we find that starting the chemical agents even after the noise exposure provides a benefit. Of course, as you would guess, starting the chemical before the noise exposure yields the best protection. So in essence, an oral medication is being developed based on strong basic science work, that can be taken before a loud noise exposure to prevent hearing loss, or in some cases, be taken shortly after a loud noise exposure to also reduce permanent noise-induced hearing loss. An important next step is that a pharmaceutical firm known as American BioHealth Group (ABG) is taking the lead in commercializing this technology and making it available for clinical trials.
AO/Beck: Dr. Kopke, this really is fascinating work and I applaud you for your knowledge and dedication to task. I hope we can get together again in the next 6 to 12 months to touch base and see how your work is progressing?
Kopke: Absolutely Dr. Beck. I would look forward to discussing this with you again and we'll be happy to keep you updated on our work.
AO/Beck: In the meantime, is there a website or two that you might recommend for people looking for more information about the Naval Medical Center and the work you do?
Kopke: Because American BioHealth Group is playing a pivotal roll in commercializing this pill; we suggest you visit their web site at www.ABGPharma.com. Interested parties can monitor the development process.
AO/Beck: Thanks Dr. Kopke.
Kopke: Thank you too Dr. Beck.
Richard D. Kopke, MD
Naval Medical Center, San Diego, California