Targeting mitochondria with ASHA-091

[Dude]

Asha Therapeutics is a company that has active programs in neuroscience for therapeutic intervention in neurodegenerative diseases including Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS), post-viral illnesses such as Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long Haul COVID.

In one of its secondary indications for the drug, Asha Therapeutics presented exciting new data for their lead Parkinson's Disease therapeutic ASHA-091 at The 12th International Biomedical Research into ME Colloquium at the Wellcome Sanger Institute in the United Kingdom. "Targeting mitochondrial dynamics is a promising therapeutic avenue to treating post-viral illnesses such as ME/CFS and Long Haul COVID," said Dr. David Asher, CEO of Asha Therapeutics.

Video in Link:

https://www.ashatherapeutics.com/post/me-cfs

 

[Elizabeth3333]

Is this the red light thing or something different?

 

[Dude]

Is this the red light thing or something different?

Nope, heres a good picture of what it "should" do:

Source: https://www.ashatherapeutics.com/pipeline

 

[Mary]

@Dude - do you know if the ASHA-091 is already being used to treat Parkinson's patients? It does look interesting, how the ASHA-091 targets mitochondrial fragmentation. I remember Bhupesh Prusty talking about how HHV6 causes mitochondrial fragmentation a few years ago.

ETA: One encouraging thing is Asha Therapeutics has a fairly accurate description of ME/CFS:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME of ME/CFS) is a devestating and debilitating post-infectious illness that is characterized by a multitude of symptoms including chronic fatigue and post-exertional malaise, brain fog, nerve pain, motor dysfunction, and many others. There is no cure for ME/CFS and relatively few treatment options beyond lifestyle and dietary changes and symptomatic therapies which are typically not robustly successful.

 

[Dude]

Yea, its even mentioned in the article:

Moreover, reactivation of viruses in patients has been linked to the onset of ME/CFS symptoms. These viral reactivation events can further induce mitochondrial fragmentation as shown below with HHV-6 and work from Bhupesh Prusty

From what i read from the pipline, its "near clinic-ready". Which i assume that soon patient trails (phase1) will start?

 

[Mary]

@Dude - just FYI, if you are replying to someone like you did with me above, it's a good idea to either tag them by putting the "@" sign in front of their name like I did with you, or like this @Mary - and that way the person will get an alert that you have responded to them.

If you "reply" to their post using the "reply" option at the bottom of their post, then that will generate an alert as well.

And if they have a lengthy post you want to reply to, instead of replying to the whole thing which will copy their entire post into your reply, you can just select a portion of it to reply to, which will again generate an alert

 

[Judee]

The only thing is it's another, "We gave mice ME and then undid it" thing. How can they give mice ME if we still are not sure what causes ME?

One encouraging thing is Asha Therapeutics has a fairly accurate description of ME/CFS

Yes, that part they did well on. I especially like how they said, "There is no cure for ME/CFS and relatively few treatment options beyond lifestyle and dietary changes and symptomatic therapies which are typically not robustly successful." [underline mine]

 

[Osaca]

The only thing is it's another, "We gave mice ME and then undid it" thing. How can they give mice ME if we still are not sure what causes ME?

Exactly and we don't even know if ME could be a strictly human thing not applicable to (humanised) mice.

If you'd want to make sure that you really gave mice ME, probably your most robust strategy currently would be to inject thousands of them first with all Herpesviruses and then months or even years later with Covid. Then you'd have to pick from the handful of mice that are still alive, those that look very unhealthy (ME/CFS symptoms), but all their values are normal. Then you could maybe guess that they have something like ME. But even then you could neither be sure, nor has anything like this ever been done, because it's a massive project.

 

[Mary]

The only thing is it's another, "We gave mice ME and then undid it" thing. How can they give mice ME if we still are not sure what causes ME?

Exactly and we don't even know if ME could be a strictly human thing not applicable to (humanised) mice.

@Judee , @Osaca - Of course you're both right about this, unfortunately! I think I got a little carried away with "hope". Obviously it would be easy to cause fatigue in mice, but that's just fatigue.

A few things that might be worth considering - Asha Therapeutics presented their material at a biomedical research colloquium sponsored by investinme.org, which I understand has a good record of sponsoring ME/CFS research. Also, even if they weren't able to induce ME in mice, I think they could induce the mitochondrial fragmentation similar to what HHV6 does in ME patients and if Asha was able to help repair that damage, it might be useful for us. So I think it's still worth following their research for that alone.

I especially like how they said, "There is no cure for ME/CFS and relatively few treatment options beyond lifestyle and dietary changes and symptomatic therapies which are typically not robustly successful." [underline mine]

That struck me as well when I first read it. They really seemed to be knowledgeable about what they said about ME/CFS which is encouraging.

 

[Osaca]

A few things that might be worth considering - Asha Therapeutics presented their material at a biomedical research colloquium sponsored by investinme.org, which I understand has a good record of sponsoring ME/CFS research. Also, even if they weren't able to induce ME in mice, I think they could induce the mitochondrial fragmentation similar to what HHV6 does in ME patients and if Asha was able to help repair that damage, it might be useful for us. So I think it's still worth following their research for that alone.

Regarding the mitochondrial fragmentation that the blood of ME/CFS patients can induce which is similar to that of HHV-6 (https://pubmed.ncbi.nlm.nih.gov/32327453/), that is something that hasn't been reproduced, right? Always makes me wonder why no one looks at this, not even Prusty or Scheibenbogen, at least in the case of Long-Covid (or possibly they have and it isn't reproducable). The Asha webiste also states that multiple studies have found mitochondrial fragmentation as a key contributor to ME/CFS pathology, but is that really the case, isn't it just Prusty's paper? It seems like Asha is quite focussed on Prusty's results in the case of ME/CFS.

I also believe Asha's progress is 100% worth following, even though success chances of early stage medication are of course very small. It would be interesting to know what exactly they presented at the conference, since a couple of drawings of mitochondria and some videos or mice aren't very enlightening.

At least it's an extremely good sign that there's a pharmaceutical company looking at ME/CFS and familiar with the disease.

 

[hapl808]

Then you'd have to pick from the handful of mice that are still alive, those that look very unhealthy (ME/CFS symptoms), but all their values are normal. Then you could maybe guess that they have something like ME. But even then you could neither be sure, nor has anything like this ever been done, because it's a massive project.

Then you'd have to take the remaining mice and tell them that nothing is wrong with them, and maybe they should just focus on doing more mazes.

As their health declines, you could do repeated unnecessary and physically draining tests and useless medical procedures on them for fun. Then encourage them to do the mazes faster - maybe they're just not trying hard enough. Give them some amphetamines and yell at them, "More mazes!! You're just lazy!" Also, try some cognitive behavioral therapy. Maybe they just need to look at mazes with a better perspective. Have them practice mindfulness and meditation.

Okay, now you've got an ME/CFS model of mice.

 

[BrightCandle]

Then you'd have to take the remaining mice and tell them that nothing is wrong with them, and maybe they should just focus on doing more mazes.

As their health declines, you could do repeated unnecessary and physically draining tests and useless medical procedures on them for fun. Then encourage them to do the mazes faster - maybe they're just not trying hard enough. Give them some amphetamines and yell at them, "More mazes!! You're just lazy!" Also, try some cognitive behavioral therapy. Maybe they just need to look at mazes with a better perspective. Have them practice mindfulness and meditation.

Okay, now you've got an ME/CFS model of mice.

You also need to get all the other mice to ignore them and steal their food. This is probably best done with electric shock therapy where the mice are promoted to steal the ill mice food but also not to go near them, its probably hard to get a mouse to just treat an ill one poorly but it can almost certainly be trained with the right amount of shock therapy.

They also need to only receive enough food and shelter if they complete the mazes and sometimes despite doing them the shelter and food/water should be withheld just for fun for a period not quite long enough to kill them but the key is its got to be cruel and random.

They need to be exposed to the outside temperatures and sometimes not get any shelter. We need to simulate the experience of no money to heat and cool a house despite their heat intolerance. Perhaps they get to choose between food or shelter for a month.

Then you are getting pretty close to the ME/CFS experience but I am sure I have missed something,

 

[Wayne]

therapeutic intervention in neurodegenerative diseases including Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS), post-viral illnesses such as Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long Haul COVID.

Hi @Dude -- Interestingly, these are all diseases that methylene blue has been purported to be helpful for. I've been researching methylene blue quite a lot the past 3-4 months, and recently started a THREAD on it here on PR. One thing I've run across is a number of interesting testimonials on the EarthClinic site. Here's one on MB being good for Parkinson's Disease:

Parkinson's Disease​

Posted by Jane (Fort Worth, TX) on 01/09/2009

​

Hi Ted,​

I am amazed that after one and a half days of taking methylene blue with vitamin c my 85 year old dad, who has Parkinson's, initiated transfer to his wheelchair and needed much less assistance than yesterday. Yesterday he was not weight bearing much. This morning I did not pick him up to get in his chair, just guided him. I broke out into laughter of happiness!​

Thank you a million for the information you provide on earthclinic. I love seeing the results!​

Jane​

 

[dr. Arf]

That struck me as well when I first read it. They really seemed to be knowledgeable about what they said about ME/CFS which is encouraging.

ASHA’s CEO wife has ME CFS

check these 2 tweets from Sam Shrivastava

https://x.com/shrivastava_sam/status/1439608854891876357?s=61&t=sKmyvHx_RteidWxD2gpxsA

https://x.com/shrivastava_sam/status/1621928604127870979?s=61&t=sKmyvHx_RteidWxD2gpxsA