Neu-002 by NeuDirection

[Nick47]

A biotech company has a new drug in preclinical development. They seem genuine, but I was not able to find any studies that support their reported results in animal models.

The fact that they cannot spell tinnitus was remarkable.

A New Dawn for the Tinnutus
By unraveling the mystery of phantom sounds, we propose a way to silence the ringing and bring relief to those who suffer from tinnitus. In a groundbreaking discovery, our team has identified a key G protein-coupled receptor (GPCR) in the auditory pathway that can transform hyperactive neurons back to their normal functioning state. We have designed a novel agonist targeting this GPCR, which has shown promising results in normalizing neuron activity. This innovative drug offers a new therapeutic approach for treating tinnitus by restoring normal auditory processing. As we advance this potential therapy, there is renewed hope for those affected by the relentless sound of tinnitus, heralding a new dawn in tinnitus research and treatment.

Neu-002 - NeuDirection

Tinnitus Tinnitus is a neurological condition characterized by the perception of noise or ringing in the ears without an external source. It affects millions of people worldwide and can range from a mild annoyance to a debilitating disorder that significantly impacts quality of life. While the...

www.neudirection.com

 

[beefling]

Their pipeline also includes Neu-003, a drug that targets epilepsy. Interesting considering our (limited) understanding of how "tinnutus" and epilepsy potentially overlap, as far as underlying neurological mechanisms go (Kv7/retigabine anyone?).

• They report data from a GPIAS (Gap-Prepulse Inhibition) model in mice, which is a standard behavioral test for tinnitus in animals.
• According to their site: > more than 50% of mice are "cured" of tinnitus in this model when treated with Neu-002.
• They also claim that over a third of the treated mice remain cured for 1 month after treatment is stopped, suggesting "permanent cure" in some animals.

Sounds okay on paper, but we all know how animal models done with mice poorly translate to humans.

A few other key points:

• Neu-002 is a small-molecule agonist for a specific, novel GPCR in the auditory pathway.
• According to their theory, tinnitus arises because of "deafferentation(?)" (loss of input) from the cochlea. This causes certain neurons to become hyperactive.
• They suggest a "parasitic oscillation loop" between the auditory cortex and the thalamus that sustains this hyperactivity.
• Neu-002 is claimed to normalize this hyperactivity by activating the GPCR, restoring more normal neural activity.
  • They say Neu-002 has a long half-life in plasma, which is helpful for a drug (it stays active longer compared to the natural neuropeptide they're mimicking).
  • Neu-002 is described as a full agonist with high affinity and selectivity for its target GPCR, meaning it ideally activates the receptor strongly and not much else.

That last point is important because taking an unfocused/shotgun approach (and, again, I'm referencing retigabine here) carries high risk with some, er... unfortunate side effects.

 

[Vincent R]

It is cool that there are biotech companies that continue to try.

However, as far as I understand it, the drug does not aim to heal the underlying cause, which is the damage to the inner ear, but instead to compensate for it by calming the neurons that react because the damaged inner ear is disrupting the input. Could that really work?

 

[hey]

I'm not sure about this one, since they spelled tinnitus wrong, but it's still great to see more and more research and attempts to cure this disease.

 

[Furetto]

I'm not sure about this one, since they spelled tinnitus wrong, but it's still great to see more and more research and attempts to cure this disease.

That is just a typo by the webmaster. The letter U is close to the letter I on the keyboard.

 

[Muggumbo]

It is cool that there are biotech companies that continue to try.

However, as far as I understand it, the drug does not aim to heal the underlying cause, which is the damage to the inner ear, but instead to compensate for it by calming the neurons that react because the damaged inner ear is disrupting the input. Could that really work?

I would assume it could work if they found a formula that is effective and safe for humans. Treating the underlying cause would be better, but having something that treats the symptoms would be the next best thing.

 

[Fields]

That is just a typo by the webmaster. The letter U is close to the letter I on the keyboard.

Indeed—it's right to next to it in a QWERTY lay-out. Moreover, it's consistently spelled correctly afterwards.

 

[Nick47]

Treating tinnitus is fine by me.

 

[beefling]

However, as far as I understand it, the drug does not aim to heal the underlying cause, which is the damage to the inner ear, but instead to compensate for it by calming the neurons that react because the damaged inner ear is disrupting the input.

This more or less sums it up. Reversing damage and "healing" anything in the auditory pathway beyond the eardrum is a
monumentally more complex and difficult task, though, and the next best thing is treating the symptoms.

Could that really work?

That's the million-dollar question, isn't it?

 

[stephenz]

Their pipeline also includes Neu-003, a drug that targets epilepsy. Interesting considering our (limited) understanding of how "tinnutus" and epilepsy potentially overlap, as far as underlying neurological mechanisms go (Kv7/retigabine anyone?).

• They report data from a GPIAS (Gap-Prepulse Inhibition) model in mice, which is a standard behavioral test for tinnitus in animals.
• According to their site: > more than 50% of mice are "cured" of tinnitus in this model when treated with Neu-002.
• They also claim that over a third of the treated mice remain cured for 1 month after treatment is stopped, suggesting "permanent cure" in some animals.

Sounds okay on paper, but we all know how animal models done with mice poorly translate to humans.

A few other key points:

• Neu-002 is a small-molecule agonist for a specific, novel GPCR in the auditory pathway.
• According to their theory, tinnitus arises because of "deafferentation(?)" (loss of input) from the cochlea. This causes certain neurons to become hyperactive.
• They suggest a "parasitic oscillation loop" between the auditory cortex and the thalamus that sustains this hyperactivity.
• Neu-002 is claimed to normalizethis hyperactivity by activating the GPCR, restoring more normal neural activity.
  • They say Neu-002 has a long half-life in plasma, which is helpful for a drug (it stays active longer compared to the natural neuropeptide they're mimicking).
  • Neu-002 is described as a full agonist with high affinity and selectivity for its target GPCR, meaning it ideally activates the receptor strongly and not much else.

That last point is important because taking an unfocused/shotgun approach (and, again, I'm referencing retigabine here) carries high risk with some, er... unfortunate side effects.

Could you elaborate on why animal models translate poorly to humans?

I remember reading about Harvard Medical School's research into regrowing hair cells in mice through gene therapy. The reason it worked in mice but will not work in humans for now is that the technique is very invasive, if not outright dangerous, because it is mostly a surgical method.

As far as I understand from the information on this webpage, Neu-002 is a drug-based solution. By definition, that should make it far more likely to translate to humans if the results are trustworthy.

If there are similar drug-based solutions that worked in mice but did not work in humans, please let me know.

A biotech company has a new drug in preclinical development. They seem genuine, but I was not able to find any studies that support their reported results in animal models.

The fact that they cannot spell tinnitus was remarkable.

Neu-002 - NeuDirection

Tinnitus Tinnitus is a neurological condition characterized by the perception of noise or ringing in the ears without an external source. It affects millions of people worldwide and can range from a mild annoyance to a debilitating disorder that significantly impacts quality of life. While the...

www.neudirection.com

I was surprised to find in the "about us" section that this is a China-based effort. I am originally from China but now live in the United States. The Chinese Academy of Sciences is very renowned, as is the City University of Hong Kong, so these look legitimate. The misspelling of tinnitus in that one instance can probably be ignored.

My family has some connections in the medical and academic fields in China, so I will ask around about these people. If this turns out to be promising, I would be glad to help share the news or help others dig up details that are not available on the English-language internet.

The Chinese clinical trial registry has quite detailed information about the Neu-001 trials conducted in Shanghai that were trying to treat amblyopia.

 

[Vincent R]

This more or less sums it up. Reversing damage and "healing" anything in the auditory pathway beyond the eardrum is a
monumentally more complex and difficult task, though, and the next best thing is treating the symptoms.

That's the million-dollar question, isn't it?

As far as treating the symptoms is concerned, I feel more optimistic about the attempts to imitate the relief that cochlear implants can provide. They aim to remove the trigger, which is the absence of input. In this case, the trigger would still be present in full force, while the drug is supposed to change how the neurons operate. Hopefully, Neu-002 will move into a clinical phase and we will learn more. Even a minor reduction in symptoms would be a significant benefit for many tinnitus sufferers.

 

[hey]

I just emailed the company to ask when they plan to start clinical trials and whether they will be open to people outside China. If anyone is interested, their email address is on their website if you want to ask.

 

[Nick47]

Could you elaborate on why animal models translate poorly to humans?

Hi @stephenz, it's a well-known fact, not just in tinnitus, but in many diseases.

I agree there always seems to be a bit of an internet blackout when it comes to some parts of the world, and we do not see the full extent of what is going on.