What substances would bring about repair of the cochlear nerve? Are there drugs devoted exclusively to this repair work that are ready or almost ready for clinical trials?
Besides true NT-3 and BDNF, several different BDNF mimetics have been identified, some of which have been newly synthesized as part of the NanoCI project. They are proteins that mimic the BDNF, with the advantage that they have longer half-life and are easier to produce and manage. There were two mimetics that were more effective than the others. One is called LMMA-2 or L2 for short, the other one is Trihydroxyflavone or THF for short.
Normal innervation
This is an illustration of a normal inner ear.
From top to bottom, you see the three ducts of the cochlea shaded in brown: scala vestibuli, scala media, scala tympani. The nerve fiber and the hair cell is shaded in green. The synapse is shaded in yellow.
CI innervation
This is an illustration of an inner ear that has received a cochlear implant.
This is not just any CI, but the very latest in CI technology. Here you see the kind of biochemical and bioengineering tricks that the NanoCI project was dealing with.
Green still represents the nerve fiber, and yellow represents the synapse. But instead of a hair cell on the other side, you see a cross section of the electrode, shaded in pink. Each synapse is an interface between a nerve fiber and an electrode contact. The synapses shaded in yellow in this illustration do not co-exist on the same plane, it just looks that way from this point of view. Remember it's a cross section.
I don't want to explain every detail. I should not have to. All the details can be found on this website:
http://www.nanoci.org/index.php
It's fascinating to see what they have accomplished. I know people on this forum are not looking for a cochlear implant. But nevertheless! The results of projects like this one are still relevant to us all. The most striking feature on the illustration above is how they were able to attract the nerve fiber to the electrode. This was done by releasing NT-3 or BDNF mimetics from a reservoir in the electrode. Really cool stuff!
The illustration only shows one nerve fiber, because it's an illustration. In real life, there would have been multiple nerve fibers connecting to multiple electrode contacts. What's also new about this CI electrode is that it has three times more contacts and channels than what we see in current CI designs.
Attraction of nerve fibers by electrical stimulation is something that professor Helge Rask Andersen of Uppsala university has been contemplating ever since he demonstrated otic nerve fiber regeneration over a decade ago. I won't say it's signed by him, but this work is clearly influenced by him.
I don't know about drugs for regrowing otic nerve fibers exclusively. But the NanoCI project may be an inroad for that. They can synthesize LMMA-2. That's a beginning of a drug. Besides, NanoCI was never about CI exclusively.
Quote from the final report:
"A total of
4 patents to protect intellectual property related to NANOCI have been filed or are in preparation at the end of the project. In addition,
over a dozen individual exploitation tracks have been identified, which will be pursued
beyond the NANOCI project. These exploitation tracks include further
developments of neurotrophin biomimetic molecules, nanomatrix gels, conductive and antibiotic nanoparticles, optic sensors,
mathematical neuron models, in vitro and in vivo bioassays (as shown in Figures 3, 4 and 5),
controlled drug-release and medical imaging technologies (as shown in Figure 6), among others."
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