AUTEN-67 as an Example of an Autophagy-Enhancing Drug Candidate

For more than a decade there has been some interest in the research community in developing treatments based on enhancing the cellular maintenance processes of autophagy. Higher levels of autophagy feature in many of the established animal lineages with modestly extended healthy longevity, created through genetic manipulation. Despite this interest, and a growing number of drug candidates, there has been little progress in moving towards trials or clinical translation, however. This paper describes another new drug candidate:

Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases, and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies.

Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stress-induced cell death. It also restores nesting behavior in a murine model of Alzheimer's disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

Link: http://dx.doi.org/10.1080/15548627.2015.1082023

Comments

Awesome. Yet another candidate which chips away at the list of things that go wrong.
So now we have (just off the top of my head):
* repair of communication with mitochondria/nuclear DNA via enhanced NAD+ - Niagen as well as mitochondria specific protection (Mitogen)
* anti-senolytic drugs
* Apoptosis-enhancing drugs
* Autophagy-enhanching drugs

Now we need others that can degrade long lasting intracellular junk such as amyloSENS and lysoSENS.

The naysayers stupdily say 50 years. We *already* have first steps in at least four of the seven identified categories of aging. Even if the initial drugs we have give us 2-3 years that's another 2-3 years in which to discover more and the pace of research is only accelerating from here on in.

Posted by: xd at May 5th, 2016 11:43 AM

@xd check out GAIM from neurophage for amyloid clearing.

Check out my research project launching on lifespan.io next week for Senolytics http://www.majormouse.org

The naysayers know nothing about what goes on in the lab or what is feasible. They can say what they like they will be first in the queue when these therapies arrive.

Posted by: Steve Hill at May 5th, 2016 5:48 PM

@XD,
I love your enthusism.

If would be nice if we could have a running total status for each of the 7 conditions that causes aging.
In other words, where are we at for each drug candidate or repair mechanism (for that condition) with regards to eventually goal of clinical studies, maybe an estimated timeline and so on.

If a progress report on say a yearly or quarterly basis for all 7 conditions, even if there no advancement for some of the 7 conditions, it would be good to show on a chart, anyway. This could include status of a company or companies that could be working on one particular condition or cause of aging.

Any thoughts or comments?

Posted by: Robert Church at May 5th, 2016 7:29 PM

@RC Thanks.

This blog is pretty good but just general science blogs like sciencedaily let you know about all the progress that's going on. I've been watching the discovery of stem cells and tissue engineering for 10 years. While we're not there yet, there has been serious progress. We haven't (as the naysayers correctly point out) created even a single fully sized organ (yet). We have, however, (as the naysayers incorrectly deny) made serious progress: we have somewhere like six organoids already functional in the lab.

Sure, if I remember I'll post a progress report from time to time.

Posted by: xd at May 5th, 2016 7:45 PM

@XD,

I actually look at the ScienceDaily every day and even Ray K, though his does not provide much info.

We love to hear new discoveries and progress and screw these idiots, Miss whats her name, their talking out of their you know what.

Thanks again XD.

And, Steve, thanks as well. We love the additional info and more updates you can provide.

I really love Reasons's blog. It provide me with hope going into the future as I suspect for others too. And, most of the comments are great, too.

Posted by: Robert Church at May 5th, 2016 8:02 PM

@Steve Hill: Awesome work. I hope you get all your funding.

Posted by: xd at May 5th, 2016 10:51 PM

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