AVL-3288 for cognitive deficits

"AVL-3288 is considered a one-of-a-kind “type 1” positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. It is in trials for the treatment of cognitive impairment associated with schizophrenia. It is thought to elicit slightly different effects than other drugs targeting the alpha-7 nicotinic receptor in that it is classified specifically as a “type 1” positive allosteric modulator (PAM).

Treatment with this drug should significantly enhance cognitive function. That said, as a “type 1” positive allosteric modulator (PAM) it will have different effects on the upregulation of alpha-7 nicotinic acetylcholine receptors than “type 2” PAMs. Preliminary research comparing type 1 and type 2 PAMs suggests that: type 2 PAMs inhibit upregulation of α7 nAChRs – whereas type 1 PAMs have no effect.

The inhibited upregulation of α7 nAChRs results in receptor desensitization, whereas no such effect is associated with type 1 PAMs like AVL-3288. As a PAM, this drug will differ from α7 nAChR agonists in that it won’t immediately enhance short-term memory or cognitive function. However, when consistently administered, the drug significantly boosts cognitive performance, and thus may be promising for those with schizophrenia (and Alzheimer’s)."

Info quoted from mental health daily

The trial is recruiting participants in New York state. This is phase 1, so a long way from proving itself.

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Well, I hope it works. I’ll be waiting.

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That sounds very promising.

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So it is in phase 1…

Just noticed that we might have news on another cognitive drug soonish - the study for RO5545965 just ended. It seems like the news after phase 1 trials is slow or non-existent. But perhaps this will also be one to keep an eye on. https://clinicaltrials.gov/ct2/show/NCT02824055

RO5545965 is a PDE10 inhibitor.Other PDE10 inhibitors are being tested, but thus far (to my knowledge) none have ultimately proven effective.

TAK-063 phase 2 trial also was completed last year. It is a PDE10A inhibitor for cognitive symptoms. No results were posted and it has disapeared from the Takeda website (so I’m going to assume it did not work, but I haven’t actually found any documentation of this). Although they do list another drug, TAK-831 a DAAO inhibitor, for schizophrenia, in phase 1.

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This is good stuff. Nicotinic a7 agonists might not work though. Remember encenicline and Aqw051.

The other one coming out soon is avn-211, i think it is a 5ht6 antagonist. Many atypicals are 5ht6 antagonists, none of them cure cognitive impairment.

Sodium benzoate also had some effect on cognition.

Some of our discoveries might be serendipitous, just like the discovery of neuroleptics.

Or drugs will fail a primary indication and instead be pursued in a secondary indication/endpt.

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Minocycline 50 mg works for severe negative symptoms but has dangerous side effects
they should investigate that med even if it’s decades old

Do you know if those a7 agonists were type 1 or type 2 PAMs? Apparently (and this is above my pay grade) AVL-3288 is a type 1 PAM and is not supposed to desensitize the receptors like the type 2s do. At least that is how I read it.

I’m not sure we’ll see any more on AVN-211 because the results apparently weren’t significant enough. There’s also a question of whether Aveneuro has the money and expertise to continue with it. But it’s possible they’ll partner with another pharma co and try and change the study parameters to get something out of it. I need to look it up again, I remember one recently which did not meet statistical significance, but the researchers speculated that this was because an effect only started to be noticed in week 6 of a 6 week study. I can’t remember if it was this drug.

http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=585503

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Wasn’t encenicline supposed to increase IQ by 10 points? Man, I sure need a drug like that.

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