Interview Of Professor Lowry William - Drug Uk5099 (study On Lactate Dehydrogenase Activity)

[Noisette]

Hey Guys

I tried to contact the main researcher who is in charge of the study : Professor Lowry William.
He answered me after his holidays.

I can send your questions about the study to his regular adress (he gives me his email).

So you're all welcome to write your questions and I can send them to the Professor Lowry.

This study " Lactate dehydrogenase activity drives hair follicle stem cell activation "


From @jo-achim

is there a way to contact the researchers who were conducting the study? to get some info on possible dosing and safety risks for human self-experimentation. they would probably be eager to know whether it works on humans or not. they are probably legally not allowed to encourage us to try on ourselves, but maybe they can help give some useful info nevertheless.
we need to try that stuff. it looks more and more promising.

From @hellouser

My first question would be if they observed miniaturized follicles with low DP cell count increase in size and DP cell count. If that's where it worked then... we have reason to get excited.

 

[Noisette]

Added to the list Miss PBB

 

[Min0]

Why didn't they apply lactate directly ? do they think that can work ? i mean, applying directly lactate on the scalp instead of using lactate raising drugs.

 

[kiwipilu]

Why didn't they apply lactate directly ? do they think that can work ? i mean, applying directly lactate on the scalp instead of using lactate raising drugs.

everybody please hold your breath ^^

 

[d3nt3dsh0v3l]

Why didn't they apply lactate directly ? do they think that can work ? i mean, applying directly lactate on the scalp instead of using lactate raising drugs.

Lol I bet it is because it's not the lactate that's the problem, but the cell's metabolism. I bet DHT causes the metabolism to go out of whack and somehow not provide the nutrients to cycle the hair; it's funny to me that DHT makes everything else grow (body hair, prostate) and DHT based steroids are very anabolic and that somehow, making the metabolism of the scalp hair cells lower by forcing fermentation instead of fully oxidizing glucose within the mitochondria makes it act normal.

Just a guess of course. But I'm keen to know the answer!

 

[Min0]

Lol I bet it is because it's not the lactate that's the problem, but the cell's metabolism. I bet DHT causes the metabolism to go out of whack and somehow not provide the nutrients to cycle the hair; it's funny to me that DHT makes everything else grow (body hair, prostate) and DHT based steroids are very anabolic and that somehow, making the metabolism of the scalp hair cells lower by forcing fermentation instead of fully oxidizing glucose within the mitochondria makes it act normal.

Just a guess of course. But I'm keen to know the answer!

ofcourse the lactate is not the problem, the lack of it in these cells is the problem.
so they used drugs that were designed to raise lactate. with two different drugs that raise lactate they got results.
i'm guessing that they were making sure that the cell gets enough lactate instead of using lactate topically and wondering wether it got there or not.

 

[AlexWrill]

Hey Guys

I tried to contact the main researcher who is in charge of the study : Professor Lowry William.
He answered me after his holidays.

I can send your questions about the study to his regular adress (he gives me his email).

So you're all welcome to write your questions and I can send them to the Professor Lowry.

This study " Lactate dehydrogenase activity drives hair follicle stem cell activation "


From @jo-achim


From @hellouser

Put simply, could UK5099 cure androgenic alopecia by allowing death follicules (aka minituarized) to born again ?

 

[d3nt3dsh0v3l]

ofcourse the lactate is not the problem, the lack of it in these cells is the problem.
so they used drugs that were designed to raise lactate. with two different drugs that raise lactate they got results.
i'm guessing that they were making sure that the cell gets enough lactate instead of using lactate topically and wondering wether it got there or not.

Er maybe I wasn't clear when I said lactate is not the problem. I wasn't saying that either the presence or absence of lactate itself is the issue. I was pointing out that it might be the change in the cell's metabolism that is responsible for the result.

Recall cellular respiration. The glucose that cells uptake are converted into pyruvate and a little energy is released. Now we can turn this pyruvate into lactic acid by fermentation when there is no oxygen and get a little more energy out. Or, we can send it to the mitochondria to completely oxidize it and get a lot more energy out. What the paper showed, essentially, is if you block the entry of pyruvate into the mitochondria or if you enhance its conversion into lactate by increasing the enzyme responsible for that pathway, hair loss gets better.

Some look at it and say "it must be the presense of the lactate that fixed it"

I am merely looking at it, and in consideration of the fact that they don't just add lactate to the cells, and I think "I know androgens can profoundly affect cellular metabolism as can many hormones. The metabolism of an organ is directly resposible for the manner in which it grows, by definition - metabolism defines the mass and energy uptake of that organ. Given that the hair's growth cycle goes out of whack in the presence of DHT, perhaps it is not the mere presence or absence of lactate alone that is the cause, but rather the dramatic shift in the cell's metabolism, that is, the very processes by which the cell uptakes and utilizes mass and energy."

Suppose that your car's gas tank had a leak. The symptoms would suggest that the car is low on gas and therefore unable to function correctly. A potential remedy would be to add more gas. In this particular case, the addition of gas would be a negligible treatment because the root cause of the issue is that the gas is taking an incorrect path - out of the car rather than into the engine. Were we to patch the hole to prevent that path, or install tubing to route the gasoline mostly to the engine as opposed to the hole, we might see improved car performance.

Now I'm not claiming that lactate itself isn't a factor. I don't have proof for that. What I am merely suggesting is that "more lactate" is just one of several possible explanations.

Just my thoughts of course. Again I have no proof. But I wanted to clarify the misunderstanding as maybe I wasn't clear the first time.

 

[Min0]

Er maybe I wasn't clear when I said lactate is not the problem. I wasn't saying that either the presence or absence of lactate itself is the issue. I was pointing out that it might be the change in the cell's metabolism that is responsible for the result.

Recall cellular respiration. The glucose that cells uptake are converted into pyruvate and a little energy is released. Now we can turn this pyruvate into lactic acid by fermentation when there is no oxygen and get a little more energy out. Or, we can send it to the mitochondria to completely oxidize it and get a lot more energy out. What the paper showed, essentially, is if you block the entry of pyruvate into the mitochondria or if you enhance its conversion into lactate by increasing the enzyme responsible for that pathway, hair loss gets better.

Some look at it and say "it must be the presense of the lactate that fixed it"

I am merely looking at it, and in consideration of the fact that they don't just add lactate to the cells, and I think "I know androgens can profoundly affect cellular metabolism as can many hormones. The metabolism of an organ is directly resposible for the manner in which it grows, by definition - metabolism defines the mass and energy uptake of that organ. Given that the hair's growth cycle goes out of whack in the presence of DHT, perhaps it is not the mere presence or absence of lactate alone that is the cause, but rather the dramatic shift in the cell's metabolism, that is, the very processes by which the cell uptakes and utilizes mass and energy."

Suppose that your car's gas tank had a leak. The symptoms would suggest that the car is low on gas and therefore unable to function correctly. A potential remedy would be to add more gas. In this particular case, the addition of gas would be a negligible treatment because the root cause of the issue is that the gas is taking an incorrect path - out of the car rather than into the engine. Were we to patch the hole to prevent that path, or install tubing to route the gasoline mostly to the engine as opposed to the hole, we might see improved car performance.

Now I'm not claiming that lactate itself isn't a factor. I don't have proof for that. What I am merely suggesting is that "more lactate" is just one of several possible explanations.

Just my thoughts of course. Again I have no proof. But I wanted to clarify the misunderstanding as maybe I wasn't clear the first time.

UCLA scientists found that HFSCs produce and consume more lactate than other cells. so they first blocked LDH and hair stopped growing.
then tried two different drugs via two different pathways to raise lactate. both different methods activated the HFSCs and grew hair.

if they used only one method you can argue that the way that drug changed the behavior of the cell is the responsible for the regrowth.
but they used two different methods to raise lactate and it worked so your theory is less probable.

 

[d3nt3dsh0v3l]

UCLA scientists found that HFSCs produce and consume more lactate than other cells. so they first blocked LDH and hair stopped growing.
then tried two different drugs via two different pathways to raise lactate. both different methods activated the HFSCs and grew hair.

if they used only one method you can argue that the way that drug changed the behavior of the cell is the responsible for the regrowth.
but they used two different methods to raise lactate and it worked so your theory is less probable.

Disagree.
Blocking LDH = no lactate production -> pyruvate has to go somewhere -> goes into mitochondria -> oxidation is enhanced and hair loss INCREASES edit: thanks to Min0 for pointing out this typo. This is what I meant to write.

The reverse approach -> block transport into mitochondria -> pyruvate has to go somewhere -> becomes lactate -> enhanced hair growth

Increase LDH activity -> fraction of pyruvate converted into lactate increases -> more hair


In each of those cases, cellular metabolism is directly affected, namely a tradeoff between respiration or fermentation.

Again it could be that lactate is directly responsible. But to me that sounds unlikely, since they didn't apply lactate directly and since I think DHT acts through the cell's metabolism. I have no proof. If excess lactate is provided from external sources and it helps hair, I might agree with you. But right now it appears that the answer is unknown.

 

[d3nt3dsh0v3l]

sounds like a good theory. i hope that prof can enlighten us soon. this lactate-story just looks too promising to not trying it out.

Yeah for sure, I'm all for people trying stuff of course!

 

[Min0]

Disagree.
Blocking LDH = no lactate production -> pyruvate has to go somewhere -> goes into mitochondria -> oxidation is enhanced and hair loss slows.

The reverse approach -> block transport into mitochondria -> pyruvate has to go somewhere -> becomes lactate -> enhanced hair growth

Increase LDH activity -> fraction of pyruvate converted into lactate increases -> more hair


In each of those cases, cellular metabolism is directly affected, namely a tradeoff between respiration or fermentation.

Again it could be that lactate is directly responsible. But to me that sounds unlikely, since they didn't apply lactate directly and since I think DHT acts through the cell's metabolism. I have no proof. If excess lactate is provided from external sources and it helps hair, I might agree with you. But right now it appears that the answer is unknown.

Blocking LDH = oxidation is enhanced and hair loss slows.
WRONG. did you read the study ? when they blocked LDH, hair didn't grow.

Blocking LDH = oxidation is enhanced and hair loss slows accelerates.

Lactate is the favorite energy source of HFSCs activity, and not pyruvate oxidation.

 

[liquidfirex]

Personally I think it's likely that lactate is acting as a mimetic to a hypoxic state which looks to be good for hair: https://www.ncbi.nlm.nih.gov/pubmed/20203417

Hypoxia->Lactate->"Growth factor cascade"

 

[d3nt3dsh0v3l]

Hey someone that speaks my language!

Yeah so I see what you're getting at. If recalled, the RK drug UCLA has patented increases the production of lactate fermentation, which increases hair growth, right? But that doesn't equate to lactate itself being responsible for growth, it could be attributed to the re-balancing of glycolisis. This is similarly found with the PGe2 angle, in that the balance of PGe2 and PGd2 was hypothesized as being responsible for hair growth, or at least moderation, respectively. So, one couldn't simply inhibit PGe2 and expect hair to grow, but would have to re attribute the balance of both of the chemicals which would be impossible to do externally.

So if you think of it as percentages, where PGe2 is at 50% and PGd2 is at 50%, you couldn't, in vitro or otherwise, reduce PGe2 by 25% and increase PGd2 25% to make it a whole 75/25 ratio. There is just no way to do that. You couldn't accurately measure that in the human body, and this is why Setipiprant will never work.

So the same goes for Lactate. Now I'm pretty convinced that Lactate holds a piece of the puzzle here, but this is why the UCLA decided to go with modifying the glycolisis process. By stimulating the fermentation process, your body will naturally balance the rest of the process out to equilibrium. The same goes with wounding, wounding releases lactate to heal the wounds and glycolisis is naturally balanced out in response to this.

Regardless, there were studies that showed different amounts of lactate did activate stem cells (as is referenced in the other forum, found by Min0, I believe) which would support the theory that there could be an approachable angle with applying lactate topically.


FOR GOOD MEASURE ILL POST MY QUESTION AGAIN:
We need to know whether there is less LDH activity in a balding mans scalp. Is there a detectable difference in LHD activity? And this should be a fairly easily testable question using rats as well.

Agreed. I posted the above in your lactate thread on one of the first few pages btw. One thing I was also asking (which is a lot to ask, I know), is if any brave soul would be willing to apply calcium pyruvate to their scalps. I think that should, uh, make things worse. But it would be good to know. For science. Someone slowly thinning maybe...? Please respond.

 

[Min0]

The thing that i hate to admit is, why is everyone in the world pretending that all hair is the same ! It is not ! And i'm not talking about species, even the position matter in humans and some primates.

Dht makes human bodyhair grow for example. But hurts scalp hair.

Scalp hair is very different, only studies done on human scalp or their dermal papilla in vitro should count.

Also all DHT LDH relation should get thrown away because if dht reduces lactate then it shouldn't grow body hair!


The closer guess is that DHT on the scalp sometimes seem to no longer promote the expression of genes that code for growth factors. That is similar to the lack of lactate causing no activation of stem cell(less growth factors?) in mice hair (which is equivalent to human bodyhair).

 

[NewUser]

Why didn't they apply lactate directly ? do they think that can work ? i mean, applying directly lactate on the scalp instead of using lactate raising drugs.

Possibly because excess lactate in the blood stream might lead to lactic acidosis. It might be best to let the body's cells produce lactate in minute amounts by drug stimulus. Just a guess.
-------

Questions: Did using RCGD423 produce any tumors, and is RCGD423 a possible candidate drug for testing in humans?

Will you be testing a topical formulation of the drug in lab experiments?

Have there been any inquiries from pharmaceutical companies?

 

[H]

I like this thread good discussion.

 

[kiwipilu]

Guys keep in mind: remove DHT out of the equation for this one, it’s not about thinning hair only /aag. The study showed the drugs promotes growth for all kinds alopecia/baldness (hormonal, stress, aging or chemotherapy..)Anyway what about body hair? would those drugs work for beard growth? Eyebrows? Is this the same mechanism Just a question I m not scientist : o…

 

[d3nt3dsh0v3l]

Blocking LDH = oxidation is enhanced and hair loss slows.
WRONG. did you read the study ? when they blocked LDH, hair didn't grow.

Blocking LDH = oxidation is enhanced and hair loss slows accelerates.

Lactate is the favorite energy source of HFSCs activity, and not pyruvate oxidation.

I read the study. It was an honest mistake. I meant hair loss increases/growth slows. Please reevaluate my point with that in mind. I have added an edit. My statements were otherwise in agreement with what you wrote above, with the exception of being convinced that exogenous supplementation of lactate will address the problem.

 

[Min0]

Guys keep in mind: remove DHT out of the equation for this one, it’s not about thinning hair only /aag. The study showed the drugs promotes growth for all kinds alopecia/baldness (hormonal, stress, aging or chemotherapy..)Anyway what about body hair? would those drugs work for beard growth? Eyebrows? Is this the same mechanism Just a question I m not scientist : o…

the equivalent of mice hair is human bodyhair. it grows with androgens, so i think that this study means nothing for our problem.
i recommend everyone to read this study :

Androgens and hair growth.
https://www.ncbi.nlm.nih.gov/pubmed/18844710

human head hair gets thinner with androgens, but other body and beard hair gets thicker !
that's why experiments on mice never work for human hair. it's like experimenting drugs on human beard ! but we know that what grows beards kills scalp hair.

the only mice that might be useful for Androgenetic Alopecia are these poor little creatures :
A mouse model of androgenetic alopecia.
https://www.ncbi.nlm.nih.gov/pubmed/20233794