Dr. Kopke has been working in this area since 1994 and initially worked to prevent and reverse hearing loss due to toxins by counteracting ROS effects.
By CDR Glen Rovig, MSC
Operational Audiology Officer
You have probably seen some recent national publicity concerning research into new types of treatment and prophylaxis for sensorineural hearing loss. Two researchers at NAVMEDCEN San Diego are working with a micro-catheter to deliver medication to the cochlear fluids via absorption through the round window. They (and others) are also looking at the contribution of free radicals to noise and toxin-induced hearing loss, and the preventive effects of antioxidants. After doing some background reading, I communicated with one of the researchers, otolaryngologist LCDR Mike Hoffer, MC, USN. He was kind enough to answer a series of questions for me, and I thought the information might be useful to the Occupational Health community.
First, a few basics:
Loud noise causes reduced microcirculation within cochlear blood vessels.
This somehow releases higher than normal numbers of radical oxygen species (ROS) or “free radicals” which can react with and damage cellular protein, DNA, and unsaturated lipids. (My grasp of autocatalytic events is a bit tenuous, so I cannot give you much clarification here.)
The body’s normal antioxidant defenses cannot counter the excess free radicals. TTS and PTS may follow with prolonged noise exposure. This is a gradual, noise-induced permanent threshold shift model, as opposed to acoustic trauma, which may physically damage the tectorial and/or basilar membranes and associated structures.
One study involving chinchillas is representative. Each animal was treated with saline (control) applied to the distal surface of one round window membrane, and an antioxidant applied to the opposite round window. The animals were then exposed to 4 kHz noise at 105 dBSPL for four hours. Antioxidant-treated ears showed significantly less TTS and reduced PTS as well as significantly less outer hair cell loss compared to the control ears.
Augmenting the antioxidant defense system with additional “free radical scavengers” holds promise for preventing/minimizing hearing loss from toxins and noise exposure.
A second area of research is delivering medications to the cochlear fluids via micro-catheter. Entering the middle ear via a small hole in the TM, the catheter is placed against the round window, where medication is absorbed through the membrane over a period of several days. A major benefit is that medication goes directly to the target area and avoids side effects associated with oral administration.
Here are LCDR Hoffer’s replies to my emailed questions:
Q: What types of patient care are being envisioned for the catheter?
A: The catheter is a FDA-approved device for irrigation of the round window membrane. We have done all of the pioneering basic research with the device and had the original and largest experiment on humans. The catheter is, however, being used for multiple indications at other (select) institutions. Most of these institutions are following protocols which we established. Indications for the catheter include, but are not limited to, Meniere’s Disease, sudden sensorineural hearing loss of a variety of etiologies, tinnitus treatment, and toxic insults to the inner ear (hearing and balance). The catheter has been used on approximately thirty patients at our institution. Six patients with sudden hearing loss have been treated. All three patients who were seen in under four weeks showed a dramatic improvement after treatment. The other three patients seen (longer time since injury) had no improvement. Contraindications to catheter use include all standard ear surgery contraindications and all contraindications to surgery. We have seen no complications directly caused by the catheter.
Q: Is there any projection to use catheters to deliver antioxidants to humans, either before or after noise exposure?
A: The treatment of inner ear disorders (hearing and balance) is a complicated issue. For many disorders the treatment depends on using the right medicine (antioxidant, etc.) and having the appropriate concentration reach the target organ at the appropriate time. If oral administration achieves this end, and surgery can be avoided, that’s fine. Undoubtedly, certain medicines (and certain antioxidants) will need to be delivered in an other than oral fashion. Severe sudden noise induced hearing loss (e.g. after a blast injury), is one example, of a disorder that may only be rescued with microcatheter delivery of antioxidants. Prophylaxis will be accomplished through some type of oral medication.
Q: The news release focuses on prednisone/steroid therapy for acute cochlear conditions. Is there an application for prednisone with NIHL? Does prednisone act the same way as an antioxidant?
A: There is basic science work that indicates that corticosteroids can rescue noise induced hearing loss and have antioxidant properties. Methylprednisolone, for example, up-regulates antioxidant enzyme activity in neural tissue. It also has other effects such as neuroprotection, increasing cochlear blood flow, and antiapoptotic and anti-inflammatory effects.
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