Treatment of inner ear tinnitus

A large number of tinnitus cases may be due to single or repeated incidents of excitotoxicity in the cochlea, which can be provoked e.g. by exposure to excessive noise, fluctuations in the blood supply to the cochlea or certain ototoxic medications. Excitotoxicity leads through the excessive release of the neurotransmitter glutamate to neural degeneration, which may in turn lead to tinnitus. While the exact mechanisms responsible for the appearance of tinnitus following excitotoxicity remain to be elucidated, it seems highly likely that some dysregulation of cochlear NMDA receptors lies at the heart of the problem. Accumulating evidence suggests that the “phantom sound” is generated by dysregulated NMDA receptors which produce aberrant firing of the auditory nerve.

Frequently asked questions

How does AM-101 work?

AM-101 is a non-competitive antagonist of NMDA receptors which blocks the unwanted activity of NMDA receptors in the cochlea. According to our hypothesis, this can suppress the aberrant excitation of the auditory nerve that is perceived as tinnitus.

For which types of tinnitus could AM-101 work?

Animal studies with AM-101 were performed in a model of tinnitus induced by acoustic trauma, a condition known to trigger glutamate excitotoxicity in the inner ear. While it does not seem unlikely that AM-101 could also work in case of tinnitus provoked by other triggers of excitotoxicity, we do not know whether this holds true at this point.

Would AM-101 work only in acute tinnitus?

The animal studies with AM-101 were performed in a model of acute acoustic trauma with treatment shortly after tinnitus onset. At this point it is unknown whether there is a therapeutic window during which AM-101 is effective, and if yes, how long such window could last. It seems likely that after some time centralization of tinnitus sets in (i.e. the brain "memorizes" the phantom sound), and a pharmacological treatment of tinnitus in the inner ear may no longer be possible. This question is the subject of much scientific discussion. In general, brain plasticity tends to be more rapid in the type of animals tested than in humans.

How is AM-101 administered?

AM-101 is administered by intratympanic injection, a slightly invasive and safe procedure that has been known and practiced by ENT doctors for several decades. For the injection, the eardrum is first locally anaesthetized, then slightly perforated with a fine needle through which the drug is administered into the middle ear. During the procedure and for 30 minutes thereafter, patients are lying with their treated ear up. This shall allow for maximum contact of the drug product with the round window membrane - it is throgh this very small membrane that AM-101 then diffuses into the inner ear and reaches its target. After the resting period, patients get up and can go home.

How safe is AM-101?

Preclinical tests in animals as well as the phase I/II clinical trial showed a good safety profile and local tolerance. In particular no effect on hearing or balance was observed. Thanks to local administration of the drug, only tiny amounts need to be administered.

When could AM-101 be available?

Like any other investigational drug, AM-101 first has to go through a certain number of clinical trials in order to thoroughly evaluate its safety and efficacy - in accordance with applicable regulations and laws. This process, involving an increasing number of participants at each subsequent study, is taking several years and a precondition for submitting a request for marketing approval. AM-101 will therefore even in the best case not be on the market shortly. It is also important to note that all drug development projects carry a substantial risk of failure, i.e. a great number of investigational products never make it to the market due to unacceptable side effects, lack of efficacy or other reasons. Therefore, market approval and general availability of AM-101 are not certain at this point.

How could I participate in a clinical trial with AM-101?

We are aware that many people are suffering very badly from their tinnitus and are eager to try out AM-101 by participating in a clinical trial. In fact, we are receiving quite many of such inquiries or requests. Please check first on our website whether a clinical trial is currently open for recruitment or not. In addition, a certain number of well-defined inclusion criteria have to be met for enrolment, while none of the various exclusion criteria are fulfilled.

Quite often, interested tinnitus patients are offering to travel very far in order to participate in a clinical trial. However, study documents may not be written in their mother tongue, which excludes them from participation - it is very important and mandatory that all study participants can read and fully understand the information provided by the clinical investigators and that they can express themselves to the investigators.

In no case can Auris Medical make any promises regarding the participation in a clinical trial with AM-101 to anyone who is contacting us for this purpose. Thank you for your understanding.