There is a hearing loss crisis in the military. Military personnel suffer from different types of hearing loss, but due to the increased exposure of military personnel to high level noise, there is more incidence of noise induced hearing loss (NIHL) in the military than in the general population. At this time, there are no drugs that are FDA approved to prevent or repair any kind of hearing loss. Our proposal addresses this deficit. The cochlea is the peripheral hearing organ. Within the cochlea, cells convert sound into electrical impulses that are carried to the brain to decode. When cells or biochemistry or anatomy of these process are disrupted, hearing loss can result. A full understanding of the molecular events underlying hearing damage is lacking. A comparison of studies reported in the scientific literature of hearing loss caused by different types of insults – high level noise, toxicity, even by sudden deafness of unknown cause - reveals that there are cellular, anatomical and molecular similarities between the different types and that specific treatment approaches can show modest effects across more than just one type. In addition, the literature suggests that the sooner a drug is delivered after the onset of hearing loss, the better the outcome will be. Although drugs to specifically attack each type of hearing loss will be valuable, it is in the common anatomical and biochemical reactions following insult to the cochlea that we may eventually find broad-based treatments. We have demonstrated in two animal models that a short treatment with the cholesterol-lowering drug fluvastatin, delivered directly into the cochlea at the time of exposure to very high level noise, prevents hearing loss and preserves cochlear structure. Pumping drugs through a catheter directly into the cochlea is an experimental approach, not a medical one. Instead, we want to develop drugs that can be ingested, allowing a patient to independently dose medication regardless of the immediate availability of medical staff, an advantage in the military. In another type of hearing loss, initiated by the cancer drug cisplatin, a preliminary report by others showed that oral lovastatin, a drug in the same statin class as fluvastatin, showed a small protection against hearing loss. In our own preliminary studies of oral lovastatin, we also show a protection (albeit incomplete) against (NIHL). We do not yet know how statins exert their effects on hearing. The effects of the statin class are not specific to cholesterol lowering. In fact, they have a broad range of effects such as antioxidant and anti-inflammatory activities and also can regulate the structure of certain cells and specific enzymes. The members of the statin class have differences in their chemistries and their biology in whole animals that can affect uptake of the drug, how long it stays in the blood, and whether it can enter the cochlea to protect or repair damaged hearing structures. Much is known about statins in humans – especially their toxicities and side effects, and this knowledge can shorten the time it takes to start using the drugs in the clinic for a new purpose. Taken together, our results and medicine’s general understanding of statins, make statins a promising drug class to treat human hearing loss. This proposal aims to further both our basic understanding of the effects of different oral statins on hearing loss, with and without steroid drugs and to compare the ability to protect hearing with the ability to protect cells within the cochlea. Concomitant with that deeper un
|Effective start/end date||9/30/20 → 9/29/23|
- U.S. Army Medical Research and Materiel Command (W81XWH2010484)
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