GW-201 aka Tetrandrine (TET) by Gateway Biotechnology (NEOMED's Jianxin Bao)

[SallyM]

This drug aims to treat tinnitus. Known by its codename GW-201, it is apparently a substance called Tetrandrine (TET).

Jianxin Bao's Gateway Biotechnology Inc recently received a grant for $972,613 from the National Institute on Deafness and Other Communication Disorders (NIDCD) which he said allows his team to work toward finding the first drug treatment for tinnitus. He is a researcher and professor of anatomy and neurobiology at Northeast Ohio Medical University (NEOMED), but also has his own company, the aforementioned Gateway Biotechnology, which has several products in the pipeline for preventing and treating noise-induced hearing loss, tinnitus, and Cisplatin ototoxicity:

But let's focus on GW-201.

We're in good hands because, according to this blog post, Dr. Bao often reads Tinnitus Talk:

"For tinnitus-related information, the two scientific websites that I check out often are: 1. Tinnitus Talk 2. PubMed"

This was the initial media coverage on him getting the almost a million-dollar grant to treat tinnitus:
NEOMED researcher receives federal grant for first human tinnitus treatment

"This generous government support will allow us to continue working toward finding the first drug treatment for tinnitus, which is a major health issue for millions of people — including the military personnel who so bravely serve our country," said Bao, who will serve as principal investigator, in a provided statement."

On the U.S. Department of Health & Human Services you can find the following details on the grant:

Award Number: R44DC018759
Targeting multiple signaling pathways for tinnitus prevention and treatment

Clicking "View Award Abstract" shows more details about GW-201 aka Tetrandrine (TET):

Possible causes of tinnitus are complicated. The current view is that hyperactivity in the central auditory nervous system contributes to the majority of tinnitus cases. This abnormal electrical activity, including an increase in delta-band activity, may be the direct result of an increase in T-type calcium channel activity. Other studies suggest that inflammatory responses within the brain may be involved in the development and persistence of tinnitus; therefore, drug candidates targeting both inflammatory and calcium signaling pathways may act synergistically to prevent and treat tinnitus.

Tetrandrine (TET), an approved drug used in China, exhibits both anti-inflammatory and calcium channel-blocking properties. Using a new tinnitus detection method in mice, we have shown that both salicylate-induced and noise-induced tinnitus can be effectively treated by TET in a dose-dependent manner.

Our hypothesis is that TET or its chemical analogs can be developed as drugs to prevent and treat tinnitus. In our proposed experiments, we have two parallel goals:

(1) obtain investigational new drug (IND)-enabling toxicity and pharmacokinetics data for TET (Aim 1) and

(2) optimize second-generation products with structure-activity relationship studies of TET and its chemical analogs (Aim 2).

Successful accomplishment of Aim 1 will enable TET to advance into clinical development. In addition, the studies of Aim 2 will enable us to identify additional candidates in case TET fails at clinical stages. By targeting multiple cellular signaling pathways that impinge upon tinnitus, our study will open new areas for the treatment and prevention of tinnitus. The extensive body of data publicly available for TET and its analogs will help us significantly reduce development time and costs.

It's interesting to note that should Tetrandrine fail at clinical stage, their strategy of optimizing second-generation products built upon Tetrandine and its chemical analogs gives them the opportunity to identify additional drug candidates that might help treat tinnitus.

What else do we know about Tetrandine?
Wikipedia says that it has anti-inflammatory, immunologic and antiallergenic effects. It's isolated from the plant Stephania tetrandra and other Chinese and Japanese herbs. It can reduce blood pressure. It's even showed therapeutic efficacy against Ebola in preliminary studies.

When you search PubMed for Tetrandine, you get 968 results, none of which mention tinnitus.

There is, however, the following paper by Dr. Bao, which is about Tetrandrine having otoprotective effects:
Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against Acoustic Trauma

When can we expect more developments?
@reggie green reached out to Gateway Biotechnology in February 2020, who then responded:

Thanks for reaching out to us. As of now, the pipeline on tinnitus is still at pre-clinical stage, so it might take another few years. Hopefully, we could get to phase III in the near future!

Best regards,
Andrea Qiu

@HootOwl also reached out to them in February, and got the following response:

It was nice to hear from you. Our company is mostly working on the prevention and treatment of noise-induced hearing loss and tinnitus developed as a result of that. As of now, we are not working on regeneration. Our drug candidates are targeting T-type calcium channel, inflammatory response pathways, and ROS/RNS. We are still raising funding to push it to the next stage of research. We also hope that hearing loss and tinnitus could be solved in the near future and our drug could benefit more people like you! Please let me know if you have any additional questions.

Best regards,
Andrea Qiu
Chief Operating Officer
Gateway Biotechnology Inc.

It's great news that only half a year later from the above correspondence they've been able to raise the additional funding.

 

[urgentresearch]

Wow! Thank you for sharing all this information, @SallyM.

 

[reggie green]

Keep hope alive, it sounds very promising. We have to hang in there.

 

[tommyd87]

Keep hope alive, it sounds very promising. We have to hang in there.

Stuff will come out. It is not going to be too far from being a reality either.

 

[asey20]

Keep hope alive, it sounds very promising. We have to hang in there.

Hell yeah. Technology advances quickly these days. This is leading to huge improvements in health/medicine as well. Gotta keep the faith alive.

 

[tommyd87]

Hell yeah. Technology advances quickly these days. This is leading to huge improvements in health/medicine as well. Gotta keep the faith alive.

The research really has advanced due to the fact that there have been big advancements in the technology. This is the big big driver as all of a sudden we are able to see stuff we have never seen before with computer modelling, devices like microscopes and other lab technology like manufacturing stuff. This will be the big boon of the treatment field in this decade.

Just look at the reasons why they have been able to advance the coronavirus drug --- because the virus can be decoded better.

 

[DebInAustralia]

This drug aims to treat tinnitus. Known by its codename GW-201, it is apparently a substance called Tetrandrine (TET).

Jianxin Bao's Gateway Biotechnology Inc recently received a grant for $972,613 from the National Institute on Deafness and Other Communication Disorders (NIDCD) which he said allows his team to work toward finding the first drug treatment for tinnitus. He is a researcher and professor of anatomy and neurobiology at Northeast Ohio Medical University (NEOMED), but also has his own company, the aforementioned Gateway Biotechnology, which has several products in the pipeline for preventing and treating noise-induced hearing loss, tinnitus, and Cisplatin ototoxicity:

View attachment 39905

But let's focus on GW-201.

We're in good hands because, according to this blog post, Dr. Bao often reads Tinnitus Talk:



This was the initial media coverage on him getting the almost a million-dollar grant to treat tinnitus:
NEOMED researcher receives federal grant for first human tinnitus treatment



On the U.S. Department of Health & Human Services you can find the following details on the grant:

Award Number: R44DC018759
Targeting multiple signaling pathways for tinnitus prevention and treatment

Clicking "View Award Abstract" shows more details about GW-201 aka Tetrandrine (TET):

It's interesting to note that should Tetrandrine fail at clinical stage, their strategy of optimizing second-generation products built upon Tetrandine and its chemical analogs gives them the opportunity to identify additional drug candidates that might help treat tinnitus.

What else do we know about Tetrandine?
Wikipedia says that it has anti-inflammatory, immunologic and antiallergenic effects. It's isolated from the plant Stephania tetrandra and other Chinese and Japanese herbs. It can reduce blood pressure. It's even showed therapeutic efficacy against Ebola in preliminary studies.

When you search PubMed for Tetrandine, you get 968 results, none of which mention tinnitus.

There is, however, the following paper by Dr. Bao, which is about Tetrandrine having otoprotective effects:
Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against Acoustic Trauma

When can we expect more developments?
@reggie green reached out to Gateway Biotechnology in February 2020, who then responded:

@HootOwl also reached out to them in February, and got the following response:

It's great news that only half a year later from the above correspondence they've been able to raise the additional funding.

The drug in question is meant to be herb (as above) derived, isn't it?

I read an abstract about the study using a herb called Stephania tetrandra that is already available in China.

Has anyone thought to try this herb?

Does anyone have any further info about how faulty calcium signalling could cause tinnitus?

 

[Piney]

Isn't this drug in clinical trials for COVID-19 caused pneumonia already?

 

[asey20]

Isn't this drug in clinical trials for COVID-19 caused pneumonia already?

This is true.

https://clinicaltrials.gov/ct2/show/NCT04308317

Feeling like this, and the Hough pill as well, are dead ends, but can't know until its tried.

 

[Silvio Sabo]

What else do we know about Tetrandine?
Wikipedia says that it has anti-inflammatory, immunologic and antiallergenic effects. It's isolated from the plant Stephania tetrandra and other Chinese and Japanese herbs. It can reduce blood pressure. It's even showed therapeutic efficacy against Ebola in preliminary studies.

Anti-inflammatory makes me believe it belongs to the same category as AM-101/Keyzilen, meaning it's geared towards treating tinnitus at the earliest stage (the so called acute phase).

 

[WillBeNimble]

Anti-inflammatory makes me believe it belongs to the same category as AM-101/Keyzilen, meaning it's geared towards treating tinnitus at the earliest stage (the so called acute phase).

I would agree it's probably treating acute. That's what most people are trying to treat, because it's what the army wants.

 

[WillBeNimble]

I would agree it's probably treating acute. That's what most people are trying to treat, because it's what the army wants.

Actually, I take that back. It's working on Calcium ion channels as well, so maybe it can help.

 

[Silvio Sabo]

Actually, I take that back. It's working on Calcium ion channels as well, so maybe it can help.

Calcium ion channels are also involved in the accrue phase. If I remember correctly release of calcium is one of the steps in the cascade of things leading to hair cell death after loud noise exposure.

 

[bmguitar]

I read an abstract about the study using a herb called Stephania tetrandra that is already available in China.

Has anyone thought to try this herb?

You can buy Stephania tetrandra (fang ji) online:
https://www.activeherb.com/extract/fangji.shtml

 

[DebInAustralia]

Are you going to try it?

 

[Joeseph Stope]

Are you going to try it?

Umm... now I see that vale of sample groups, control groups and placebo tests.

 

[bmguitar]

Are you going to try it?

According to Wiki:

The root contains many isoquinoline alkaloids: tetrandrine (0.6-0.9%), fangchinoline (0.5%), cyclanoline (0.1%) and dimethyltetrandrine iodide (muscle relaxant). The root also contains flavanoids. The main active alkaloids are: tetrandrine (12 to 23 grams/kg) and fangchinoline (0.3–3 mg/kg).​

Looks like the herb only contains very small amount of tetrandrine, so not sure if it will be potent enough. Regardless, my local Chinese herbal store has it so I might give it a go...

 

[Pete88]

Looks like the herb only contains very small amount of tetrandrine, so not sure if it will be potent enough. Regardless, my local Chinese herbal store has it so I might give it a go...

Any updates?

 

[sssing]

According to Wiki:

The root contains many isoquinoline alkaloids: tetrandrine (0.6-0.9%), fangchinoline (0.5%), cyclanoline (0.1%) and dimethyltetrandrine iodide (muscle relaxant). The root also contains flavanoids. The main active alkaloids are: tetrandrine (12 to 23 grams/kg) and fangchinoline (0.3–3 mg/kg).​

Looks like the herb only contains very small amount of tetrandrine, so not sure if it will be potent enough. Regardless, my local Chinese herbal store has it so I might give it a go...

The herb is reported to be poisonous if consumed in large amounts.

 

[bmguitar]

Any updates?

Only took it for about a couple of weeks and didn't see any benefits.

 

[Nick47]

→ Identifying Molecular Pathways Underlying Noise-Induced Tinnitus

Small thesis/animal study using Tetrandrine. Positive results.

 

[ploughna]

Some updates on their tinnitus related product pipeline:

https://www.gatewaybiotechnology.com/services/

 

[ploughna]

Regarding the above pipeline for three tinnitus drugs, it's interesting to note that with their GW-TT2 candidate they talk about repurposing existing FDA approved drugs for tinnitus via nasal delivery. GW-TT23 is also nasal delivery, and GX-TT5 is based on gene therapy.

Patents pending, so no mention of what the existing approved drugs might be unfortunately. Hopefully more news to come from these folks soon.

 

[ErikaS]

I called the number provided on the Gateway Biotechnology's website. Someone answered the phone very informally just saying hello. I honestly thought I had the wrong number. But no, it was Gateway Biotechnology. I asked about the updates to the pipeline, specifically the nasal spray (GWTT2) and he said they got positive response from the FDA last October, but they still had to compound/make the drug in a nasal solution and still have to present that, so "still probably 1-2 years away from human trials".

They do not have any kind of compassionate use program as they are a "small biotech company".

The existing drug mentioned earlier on in this thread is Tetrandrine.

 

[Ryan Scott]

I called the number provided on the Gateway Biotechnology's website. Someone answered the phone very informally just saying hello. I honestly thought I had the wrong number. But no, it was Gateway Biotechnology. I asked about the updates to the pipeline, specifically the nasal spray (GWTT2) and he said they got positive response from the FDA last October, but they still had to compound/make the drug in a nasal solution and still have to present that, so "still probably 1-2 years away from human trials".

They do not have any kind of compassionate use program as they are a "small biotech company".

The existing drug mentioned earlier on in this thread is Tetrandrine.

The sense of urgency with tinnitus research from pharma and universities is appalling to say the least.

 

[Nick47]

It seems T type calcium channels are the main target. I read lots about anti-inflammatory molecules with a meh. Specific calcium channels may be partly key though.

Interestingly, L type calcium channels were important in the previously mentioned thesis and not the T type.

 

[Travis Henry]

The sense of urgency with tinnitus research from pharma and universities is appalling to say the least.

It's murderous.

 

[ccm302]

I've also been in contact with Dr. Bao (I got the same answer as @ErikaS). From everything I've read and with him having dealings with the US Army in other trials, it seems like this may have a good chance of succeeding. I'll say what several of us have said about every other treatment - I'm surprised this doesn't have more attention. That said (and I'm sure it won't go far), I have written to my senators and representatives about these, other drugs, and name dropped the doctors involved in efforts of pushing for more funding and research to help speed up the process.

Do we know if anyone on Tinnitus Talk has other conditions that would require the use of these drugs (Tetrandrine, Nimodipine) and have anecdotally seen improvements? That would be interesting.

 

[StoneInFocus]

I've also been in contact with Dr. Bao (I got the same answer as @ErikaS). From everything I've read and with him having dealings with the US Army in other trials, it seems like this may have a good chance of succeeding. I'll say what several of us have said about every other treatment - I'm surprised this doesn't have more attention. That said (and I'm sure it won't go far), I have written to my senators and representatives about these, other drugs, and name dropped the doctors involved in efforts of pushing for more funding and research to help speed up the process.

Do we know if anyone on Tinnitus Talk has other conditions that would require the use of these drugs (Tetrandrine, Nimodipine) and have anecdotally seen improvements? That would be interesting.

I like your efforts.

I personally hope Tetrandrine/Stephania Tetrandra extract becomes commercially available as a supplement.

What is the company doing in regards to Nimodipine?

 

[ccm302]

I like your efforts.

I personally hope Tetrandrine/Stephania Tetrandra extract becomes commercially available as a supplement.

What is the company doing in regards to Nimodipine?

From what I understood (I'm a mechanical engineer, so my understanding of chemistry is limited), it seems like they were trialing it in combination with and independently of the Tetrandrine to see what it would do. It's a long read. Interestingly, the patent expiration was extended.

https://patents.google.com/patent/US10434097B1/en