SciFluor Receives US Patent for KCNQ2/3 Activator to Treat Epilepsy and Neurological Disorders

#61
guys

anyone of us have contact with a lab to make our own sf... similar pills?

there is hundreds of labs in asia either india or china who could be able to make this

what do you think of the idea?
 
#62
exodus said:
guys

anyone of us have contact with a lab to make our own sf... similar pills?

there is hundreds of labs in asia either india or china who could be able to make this

what do you think of the idea?
Click to expand...
Or we could ask my unkle Walt. He has a RV and we could synthesis something out in the desert.

No, seriously I like the idea, but it sounds kinda risky maybe.
 
#63
There are some more articles doing the rounds about SF0034. I thought about creating a new thread but it's probably better to keep everything under one hood:

http://scitechdaily.com/new-drug-quiet-brain-relieving-epilepsy-tinnitus/
http://www.eurekalert.org/pub_releases/2015-06/uoc-qtr062315.php
http://www.ncbi.nlm.nih.gov/pubmed/26063916

Autifony's drug AUT00063 targets Kv3 channels however SF0034 targets Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3) channels. I think both drugs have a good potential however SF0034 seems really promising and is 5 times more potent than retigabine/ezogabine without the nasty side effects. Professor Tzounopoulos and co published an article a couple of years ago about reduction of Kv7.2/3 channel activity playing a key role in the induction of tinnitus and it's the same Professor Tzounopoulos and co who are behind SF0034:

http://www.ncbi.nlm.nih.gov/pubmed/23716673

My only worry is SF0034 appears to be touted as an anti-epileptic drug and I hope any trials of the drug are not limited to epileptic patients.
 
#64
i know of at least one person that went with a chinese pharmaceutical synthesizer (certified by the CFDA - chinese food and drug administration - for what its worth). this person confirmed from a professional chemical analysis that it was 100% pure (retigabine). and it looks like the fluorination process is straightforward so this is definitely something that any lab can synthesize.
the issue comes with dosing, since unlike retigabine, this compound has not been tested at all in humans. given it's potency, anyone that goes down this route would have to be very careful with dosage and go very slowly. but if someone is truly looking for relief from a bad case, i think it is reasonable to consider this route.
 
#66
ruben ruiz said:
"Prevents the development of Tinnitus."
Am I missing something here. How would this affect those (us) all ready with the T?
Does any one have an idea?
Click to expand...

Well, the KV7 channels are dysfunctional after the induction of tinnitus and trobalt normalises those channels thus preventing the development of tinnitus. The KV3 channels are more important for chronic tinntus and are the correct target for tinntus. I would trust Doctor Charles Large, he knows what he's doing.
 
#67
Danny Boy said:
Well, the KV7 channels are dysfunctional after the induction of tinnitus and trobalt normalises those channels thus preventing the development of tinnitus. The KV3 channels are more important for chronic tinntus and are the correct target for tinntus. I would trust Doctor Charles Large, he knows what he's doing.
Click to expand...

Good thing his name is Charles and not Richard :p

No but seriously. I have high hopes for Autifony. I believe that they are on the right track. It's just a matter of time before we have a treatment.
 
#74
ruben ruiz said:
Some peace without feeling like a zombie would be the biggest blessing. Can you imagine the T volume down to 1 or 2
what about H?
Click to expand...
yes, i`m on RTG now and it does make you a bit distant from things ... some words in the article like `less toxic` still make me a bit worried about our future ... I mean if we have to take these things for life they better not be unhealthy like RTG.

The article explains the workings of potassium channels very well ... but my question is .. WHY arn`t they working properly in our system.

KCNQ potassium channels are found in the initial segment of axons, long nerve fibers that reach out and almost, but don't quite, touch other cells. The gap between the axon and the other cell is called a synapse. When the cell wants to signal to the axon, it floods the synapse with sodium ions to create an electrical potential. When that electrical potential goes on too long, or gets out of hand, the KCNQ potassium channel kicks in. It opens, potassium ions flood out, and the sodium-induced electrical potential shuts down. In some types of epilepsy, the KCNQ potassium channels have trouble opening and shutting down runaway electrical potentials in the nerve synapse. Retigabine helps them open.

so yes, what is the step before all of this that has decided that these little gates don`t open and close the way they should.

it`s like a gate that has trouble opening and closing and you come with a forced entry to open or close them ... but did anyone look at the mechanisms and why they arn`t fucntioning properly? anyone know more about the step before all of this? @benryu ? dude come back :)
 
#75
nills said:
The article explains the workings of potassium channels very well ... but my question is .. WHY arn`t they working properly in our system.
Click to expand...

There is evidence that there is damage to the synapses between the hair cells and the auditory nerve after inner ear trauma most likely caused by excess glutamate. AM-101 aims to lessen that damage.

If synapses are damaged then nerve fibers cannot be properly stimulated anymore. Potassium channels remain closed since no electrical stimulation is received.
 
#76
Nucleo said:
There is evidence that there is damage to the synapses between the hair cells and the auditory nerve after inner ear trauma most likely caused by excess glutamate. AM-101 aims to lessen that damage.

If synapses are damaged then nerve fibers cannot be properly stimulated anymore. Potassium channels remain closed since no electrical stimulation is received.
Click to expand...
Should i try am101 with tinnitus from ear syringing/middle ear infection/ototoxic antibiotic?
I dont want to get into trials if there is 0 reason to do that as ear puncturing is pretty invasive but if its reasonable i would consider it. What would you do with your knowledge and with my case?
 
#77
Nucleo said:
There is evidence that there is damage to the synapses between the hair cells and the auditory nerve after inner ear trauma most likely caused by excess glutamate. AM-101 aims to lessen that damage.

If synapses are damaged then nerve fibers cannot be properly stimulated anymore. Potassium channels remain closed since no electrical stimulation is received.
Click to expand...
So what if they remained open .. .would this solve our situation? don`t even know if it is possible just want to understand the mechanisms.
 
#78
nills said:
So what if they remained open .. .would this solve our situation? don`t even know if it is possible just want to understand the mechanisms.
Click to expand...

I think it would still lead to problems as well, maybe not tinnitus. The neurons would be the opposite of hyperactive. If the potassium channels remain open all the time it will become impossible to build up an electrical potential across the neuron membranes. Thus, they will become largely inactive, unable to fire new action potentials.

This is obviously a very simplistic view of the whole picture. There are not only K+ channels into play.
 
#79
Nucleo said:
I think it would still lead to problems as well, maybe not tinnitus. The neurons would be the opposite of hyperactive. If the potassium channels remain open all the time it will become impossible to build up an electrical potential across the neuron membranes. Thus, they will become largely inactive, unable to fire new action potentials.

This is obviously a very simplistic view of the who picture. There are not only K+ channels into play.
Click to expand...
ah yes, ofcourse ... there needs to be polarity for current to run so it can activate or deactivate when needed ... or something like that ... I`m still at the simplistic level of understanding all of this ... but really thanks for your view on it!
 
#80
I for one have more hope for this drug than for the autonify drug. It just sucks that it isn't as far into the process as autonify and will likely only be trailed for epilepsy. So definitely a long road ahead
 
#81
I know perhaps this has all ready been discussed on TT, but I have just read this and thought it might be useful to post it here.

A few weeks after I first got tinnitus, I spoke to a hospital doctor and told her that it felt like a kind of 'auditory' epilepsy, but I think she misunderstood, as she replied - 'you don't have epilepsy' - I don't think she heard me say the word 'auditory'.

http://today.uconn.edu/2015/06/quiet-that-ringing-in-the-brain/
 
#84
IMPORTANT INFORMATION REGARDING SciFluor Life Sciences

The hedge fund Kerrisdale Capital has recently released a damaging assessment on Allied Minds and their business portfolio (which includes SciFluor Life Sciences with SF0034 in its pipeline). Page 6 of the report reads:
SciFluor Life Sciences, valued by Allied Minds at $116 million, has two pre-clinical drug candidates and a high-level concept of using advanced fluorination chemistry to create improved versions of existing drugs. But the concept makes little sense: expert fluorination chemists have no special insight into biology or the drug market and thus have no particular edge when it comes to finding compounds that fluorination would render more valuable. By contrast, drug-development professionals are already fully aware of the potential benefits of fluorination and often consider it during their existing research processes, suggesting an absence of low-hanging fruit. Sure enough, SciFluor has struggled since its 2010 founding, failing to attract commercial interest in its fluorination reagents and undergoing a round of layoffs. Its lead drug candidate is a knock-off of an epilepsy drug that has a unique mechanism of action but no incremental efficacy relative to available alternatives, resulting in a lukewarm commercial reception and only $13 million of annual revenue before additional concerns about serious side effects emerged. SciFluor now claims that its version of the drug won't have those side effects, but in the case of the most alarming ones – skin discoloration and potential ocular damage – SciFluor's development of its drug predates the discovery of the side effects. SciFluor has presented no clinical evidence to support its assertion that the fluorinated version of the drug won't face similar problems.
Click to expand...
On the one hand, I can - on a high level - agree/sympathize with the overall assessment that KC is making - also in relation to fluorination of an existing drug (this is indeed known to be pursued for drug development). However, on the other hand, it just so happens that for SF0034, specifically, a research paper was co-authored on it by the well-known tinnitus researcher Prof. Tzounopoulos. The paper was released in June, 2015:

www.ncbi.nlm.nih.gov/pubmed/26063916

Since the paper is peer reviewed before being accepted for publication, I can only assume that it lives up to the highest standards of science. For this reason, I decided to contact KC (Mr. Sean Donohue) this Monday where I provided him with a full text copy of the paper while displaying a neutral stance to their assessment of SciFluor, but at the same time questioning if they indeed had "considered all available material" before releasing their report. Not surprisingly, I have not received a reply from KC. I decided also to follow-up with Prof. Tzounopoulos whom I have previously corresponded with (on an ad-hoc basis). Again, no reply. Previously, and shortly before x'mas last year, I had received the following update from him:
Dear Jakob,
Thank you for your interest in my research. There is one tinnitus update that I would like to share with you: we have developed and tested a novel and more specific Kv7.2/3 (KCNQ2/3) activator that works much better than retigabine both for epilepsy and for tinnitus. This novel Kv7.2/3 activator is more specific than retigabine and is less toxic, but keep in mind that all this work has been performed only in mice and rats. The manuscript describing this work in detail will be submitted for publication within the next month or so and I hope that the new compound will hopefully go to clinical trials soon.
I am not an MD and therefore clinical trials, effects of drugs on tinnitus sufferers, medical advice, and clinical applications of my findings in humans are outside of my expertise/control. I know the exact MOA of retigabine on Kv7 channels (you can read it in my 2013 publication in PNAS and in other papers such as Tatulian et al., 2001), but I do not know the MOA of retigabine on tinnitus and therefore I can not answer your question.
Best,
Thanos Tzounopoulos, PhD
Click to expand...
The "novel and more specific" compound referred to, above, turned out to be SF0034. I can therefore (again) only assume that the work behind SF0034 is solid (at least to the extent that any piece of science at the preclinical stage is solid).

Why does this matter to you? Well, following the release of the report, the stock price of Allied Minds took a fall...

www.thisismoney.co.uk/money/markets/article-3248050/Investors-suffer-heavy-losses-hedge-fund-launches-blistering-attack-Allied-Minds.html

...which in itself is serious (needless to say). It may also complicate future funding of SciFluor (for clinical trials) - which - also is serious (needless to say). It also matters to you because:
  1. Either KC has a valid point in their assessment (which means the science of SciFluor is not as robust as could be hoped for), or
  2. KC is not fully accurate in their assessment (which means SciFluor suffers unnecessarily which could ultimately affect the tinnitus community).
One article did attack KC while pointing out that their assessment was unjustified to some degree:

http://ftalphaville.ft.com/2015/09/22/2140560/allied-minds-maligned

A number of questions do remain, however:
  • Why did Dr. Charles Large (previously Director of Molecular and Cellular Biology at GSK) pursue a drug not targeting the Kv7.x channels for the treatment of tinnitus (when he came from a company that produces Trobalt, a Kv7.x channel opener)?
  • If indeed SF0034 is as effective as it is claimed to be, why did GSK themselves not pursue this avenue of drug development?
  • Which of the two sets of channels, Kv3.x or Kv7.x, would present a superior target for the treatment of tinnitus?
I attempted to get some insights to the questions above via a professor of pharmacology. The reply was rather short and did - to me - not inspire strong confidence in relation to the Kv-channel research being undertaken by the pharma companies (essentially saying that there may not be a rationale behind the research and specific targets, and also, that it is more a matter of applying the existing research to see if it can be used for other medical conditions such as tinnitus). There are also parts of the tinnitus community which is questioning the preclinical animal studies of tinnitus (due to the GAP detection model employed). This also does not inspire confidence. This re-iterates the need for "human testing" to find out if Kv7.x channel openers have any effect in relation to the suppression of symptoms of tinnitus - and - which at the moment is only possible to explore via Trobalt (an initiative undertaken by "Team Trobalt" - of which I am a former member).

It is rare for me to comment on anything in public (anymore). I only do so when things are important.

attheedgeofscience
08/OCT/2015.

[Report by Kerrisdale Capital attached].
 

Attachments

  • Allied-Minds-Report (Kerrisdale Capital).pdf
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#86
attheedgeofscience said:
  • Why did Dr. Charles Large (previously Director of Molecular and Cellular Biology at GSK) pursue a drug not targeting the Kv7.x channels for the treatment of tinnitus (when he came from a company that produces Trobalt, a Kv7.x channel opener)?
  • If indeed SF0034 is as effective as it is claimed to be, why did GSK themselves not pursue this avenue of drug development?
  • Which of the two sets of channels, Kv3.x or Kv7.x, would present a superior target for the treatment of tinnitus?
Click to expand...

This questions were very doubtful for me as well.
But I thought that combo use of SF and AUT would be beneficial for most of t suffers.

attheedgeofscience said:
This re-iterates the need for "human testing" to find out if Kv7.x channel openers have any effect in relation to the suppression of symptoms of tinnitus
Click to expand...

Personally I have no doubts that Kv channels have effect, doubt is which one, Kv7.x or Kv3.x or maybe some other too. Or all them together, but in different intensity from person to person.

So many questions, that's why is dangerous to put all eggs in one basket - AUT63... :/
 
#87
Excuse my ignorance. I know nothing about financial markets, well, usually the money is coward and goes to where the opportunity is. If I understand correctly, this KC attack on Allied Minds implies that the funding will be diminished in the next years and there are less chances of having SF0034 on the market in the next few years. Is that right?

And about the whole Kv-gate, I can only hypothesize that retigabine is, for now, the only effective Kv7.x modulator and, because its nasty side effects or patent issues, GSK are moving towards something safer, even if it's focused on another Kv channel set, as @markoana suggests. Well, in my opinion, at the end most of us will be mixing retigabine, AUT, the VNS devices or any other treatment all together, it already happens in other conditions. Of course, they have figured out that this approach might be (one of the) correct ones.

In my opinion, either retigabine has a formidable placebo effect and, since people are highly suggestionable, and much more when a lot of us are struggling, or there is something real behind this approximation to the problem. The retigabine thread is really interesting, everyday more and more people is getting, at least, temporary relief and this is the only thing that matters. A double blinded trial of retigabine for tinnitus is really needed as now.

@markoana Sadly, I've seeing a lot of new (acute) sufferers in the last months, mostly by acoustic trauma due to loud music or bad colds. Those people will become chronic in the next months, and this problem will become bigger and bigger with time. Is up to them to take advantage of the current situation (yes, you, investors and pharma guys).

Just ranting.

End of the offtopic :)
 
#88
Yes, there is a possibility that SF0034 will never come to market. This does not bode well for Allied Minds as there does not seem to be confidence in the research (or lack there of as reasoned by KC) behind it, the drug itself and whether or not they can make money off of it which is #1 from an investor standpoint. When the money dries up, so goes any chance of this being developed.
 
#90
randomuser said:
Excuse my ignorance. I know nothing about financial markets, well, usually the money is coward and goes to where the opportunity is. If I understand correctly, this KC attack on Allied Minds implies that the funding will be diminished in the next years and there are less chances of having SF0034 on the market in the next few years. Is that right?

And about the whole Kv-gate, I can only hypothesize that retigabine is, for now, the only effective Kv7.x modulator and, because its nasty side effects or patent issues, GSK are moving towards something safer, even if it's focused on another Kv channel set, as @markoana suggests. Well, in my opinion, at the end most of us will be mixing retigabine, AUT, the VNS devices or any other treatment all together, it already happens in other conditions. Of course, they have figured out that this approach might be (one of the) correct ones.

In my opinion, either retigabine has a formidable placebo effect and, since people are highly suggestionable, and much more when a lot of us are struggling, or there is something real behind this approximation to the problem. The retigabine thread is really interesting, everyday more and more people is getting, at least, temporary relief and this is the only thing that matters. A double blinded trial of retigabine for tinnitus is really needed as now.

@markoana Sadly, I've seeing a lot of new (acute) sufferers in the last months, mostly by acoustic trauma due to loud music or bad colds. Those people will become chronic in the next months, and this problem will become bigger and bigger with time. Is up to them to take advantage of the current situation (yes, you, investors and pharma guys).

Just ranting.

End of the offtopic :)
Click to expand...
What do you mean "take advantage of the current situation?" We have one person fully cured by Trobalt and it was @Danny Boy, who took Trobalt with a bunch of other drugs over the course of like a year. We also have MPT who got down to a very faint sea shell noise. Both of them did NOT get their T from noise.

Anyone that is an acute sufferer should not go into taking Trobalt thinking it's going to permanently cure them. It's an extremely dangerous drug and may or may not permanently help. It also has the possibility of permanently giving a nasty side effect.

The current situation for acute sufferers leaves few options. Trobalt if on the absolute edge, but I'm not convinced that if every acute sufferer started taking Trobalt, they'd all be cured before their T turned chronic.
 

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