Knopp Biosciences

[attheedgeofscience]

As members of this forum may know we, [USERGROUP=11]@Team Trobalt[/USERGROUP], are tracking down information on pharmaceuticals involved in potassium channel modulator research. Knopp Biosciences is (probably) another pharmaceutical that most people are not aware of. However, tinnitus is actually mentioned (briefly) on their homepage:

http://knoppbio.com/research/show.php?2

Their product pipeline shows the following drug candidates...

...and I have managed to track down that the "Kv7 platform" probably refers to the following compound(s):

IMIDAZO(4,5-B) PYRIDIN-2-YL AMIDES (as KV7 CHANNEL ACTIVATORS)

Knopp Biosciences has filed a patent application last year (see attachment) which, again, I believe is concerned with the drug candidate behind the mentioned "Kv7 platform" in the above overview. Interestingly, Trobalt/Retigabine is mentioned within the application.

As with SciFluor, we will be attempting to contact a senior representative of the company to see if we can get a few more specifics.

attheedgeofscience
19/MAY/2015.

 

[Calories]

They are yet to start animal model studies for tinnitus, So anything from them for tinnitus is at least 15 years away!

 

[Nucleo]

They are yet to start animal model studies for tinnitus, So anything from them for tinnitus is at least 15 years away

Well to be fair, it's not like anyone else is significantly more advanced in the field of tinnitus.

 

[Nucleo]

Interesting that they are pursuing dexpramipexole for treatment of ALS. Biogen Idec cancelled the project due to poor results in Phase III of their trials with this very same compound.

 

[attheedgeofscience]

Presentation by Knopp Biosciences from 2015 (concerning Kv7-channel openers). Several of the researchers working at Knopp are former students of the faculty of chemistry at Pittsburgh University (Prof. Peter Wipf) which jointly produced the research on RL-81 together with Prof. Tzounopoulos.

Tags: @sharonr @Paulmanlike

 

[jer]

Thank you very much for providing this information and keeping us all updated @attheedgeofscience

 

[Mic]

Good news... but it is still wise not to launch kv7 regulating drugs as the new holy promise of tinnitus treatment.

Back in 2011 there was an experiment in which Maxipost and it's R-enantiomer (opposite) were both effective in reducing salicylate induced tinnitus in animals. The theory was that the R-enantiomer should induce tinnitus because it opens the gates of kv7.2-7.5 channels. Instead it reduced tinnitus on the same manner as Maxipost.

Retigabine was a cannon that destroyed tinnitus... but also everything else on his way. Instead of a cannon we need a silver bullet that can be pinpointed exactly to the root of the problem.

Read more about the Maxipost experiment here:
https://www.ncbi.nlm.nih.gov/pubmed/21640740

 

[Danny Boy]

Good news... but it is still wise not to launch kv7 regulating drugs as the new holy promise of tinnitus treatment.

Back in 2011 there was an experiment in which Maxipost and it's R-enantiomer (opposite) were both effective in reducing salicylate induced tinnitus in animals. The theory was that the R-enantiomer should induce tinnitus because it opens the gates of kv7.2-7.5 channels. Instead it reduced tinnitus on the same manner as Maxipost.

Retigabine was a cannon that destroyed tinnitus... but also everything else on his way. Instead of a cannon we need a silver bullet that can be pinpointed exactly to the root of the problem.

Read more about the Maxipost experiment here:
https://www.ncbi.nlm.nih.gov/pubmed/21640740

That's from their website.
"ION CHANNEL BIOLOGY
Pursuing Novel Drug Treatments
Ion channels, proteins that regulate the excitability of cells, represent an important class of drug targets. Drugs that modulate ion channels play an important role in treating a variety of neurological and cardiovascular conditions. Among ion channel targets, potassium channels play a key role in the pathophysiology of neuropathic pain, epilepsy, and other unmet needs in diseases of the nervous system.

Knopp has reached the lead optimization stage of identifying novel selective modulators of a voltage-gated potassium channel family known as KCNQ2, building on the significant experience of its scientific leadership in characterizing and exploiting the pharmacology of this target. The KCNQ2 program provides the opportunity to secure composition-of-matter patent positions for development candidates. Knopp chemists have synthesized a library of novel compounds that modulate ion channel activity relevant in indications of persistent unmet need related to neuronal excitability.

• In neonatal encephalopathy we are targeting KCNQ2 gene mutations associated with seizures and profound developmental effects.
• In neuropathic pain, we are using translational studies to better understand potassium channel profiles in specific pain indications and to explore the potential for topical skin administration as well as oral administration.
• In epilepsy, we have synthesized channel-subtype selective agents with improved potency vs. ezogabine, the only approved KCNQ2 channel modulator, with the goal of an improved safety profile and one-daily oral dosing.
• In tinnitus, we are developing potent channel-subtype activators for proof-of-concept studies in animal models."

So I have no clue what they are targeting in tinnitus channels.

 

[Mic]

In tinnitus, we are developing potent channel-subtype activators for proof-of-concept studies in animal models

This confirms my earlier post. They have no clue if kv7.2 channels are the holy grail for T, but the fact that Retigabine did something for some people is a lead they are pursuing with animal models.

 

[Danny Boy]

This confirms my earlier post. They have no clue if kv7.2 channels are the holy grail for T, but the fact that Retigabine did something for some people is a lead they are pursuing with animal models.

Trobalt definitely worked, but had an higher affinity towards GABA vs the Potassium channels. Plus the side-effects were extreme! I'd warn anyone off that stuff. If they get Visual Snow, it could be worse than tinnitus. Too risky.

 

[Greg Sacramento]

It may come down to neuropathic pain and many researchers now believe more than what's in this link: http://discovermagazine.com/2010/oct/26-ringing-in-the-ears-goes-much-deeper
The hippocampus and it' connection to the forefront areas of the brain shows emotional stress. http://lab.rockefeller.edu/mcewen/stresshippo

It may be that one of the new class psych drugs coming to market may be our hope. I will be seeing a pain management doctor that will use filtered music matching with simulation beginning with my vagus nerve. He said that he has excellent results, but I know nothing about filtered matching music. @Steve.

 

[Paulmanlike]

@Greg Sacramento Are you talking about these new ad meds that are bring trialled that target the hippocampus? I think you previously said "a cure may of already been found" but when I researched these drugs I found no mention of tinnitus being an indication for one of these drugs

 

[Greg Sacramento]

@Paulmanlike When I was taking a particular physiology course in college, the professor, a doctor said "the brain doesn't give orders, it accept orders." He said that "this course will be about how the human body reacts to our eight body systems and hypertension was at the heart and physical heart of well being." I still have these notes.

There's at least 200 things that can cause tinnitus with many sub groups and most of the time it includes auditory and physical mechanics. Hypertension relates to cardiovascular, the nervous system, turbulent blood flow, oxygen, toxic chemicals and drugs, fatigue, depression, anxiety and the list goes on. There's no doubt that over half of the causes of tinnitus have a hypertension mental health influence.

I contacted one of the companies that has a promising non benzo brain drug and received a response. "We do not comment on future research without using a public informative format". I can understand that, as this company is public. Actually I knew that, but I tried anyways. So I contacted some medical professionals and they feel that this drug could safety lower tinnitus perception and just maybe volume. In reading their brain study literature and the parts of the brain for target, like the hippocampus, I think that it is possible that they are considering a tinnitus trial.

 

[grate_biff]

I contacted one of the companies that has a promising non benzo brain drug

they feel that this drug could safety lower tinnitus perception and just maybe volume.

Maybe they have found a way to settle down the fusiform cells in the cochlear nucleus without affecting the GABA-receptors?

 

[Greg Sacramento]

@grate_biff @Paulmanlike

https://www.sagerx.com/science.php

With SciFluor - They are hard at work on age-related macular degeneration, but they haven't forgotten about tinnitus. It may be that they are waiting for a partner to deeply engage with a venture.

From many of the neuro sites that I visit, there's is a lot of discussion on the brain per tinnitus, but I consider it just talk for now. Neuro researchers need more free money where there's not a profit incentive from others.

 

[Nobody19]

They are working on a Kv7 modulator (only in discovery so far) for "hearing disorders".

https://www.knoppbio.com/healthcare-professionals/pipeline/