Did UCLA Just Cure Baldness With PP405

[OtyMac]

Did UCLA Just Cure Baldness?

How Bruin genetic scientists are reawakening hibernating follicles.

newsroom.ucla.edu

Could a full head of hair soon be the norm ... for everyone?


In scientific terms, the PP405 molecule is isolated and applied to a protein in the follicle stem cells that keeps the cells dormant. This inhibits the protein, and the stem cells are moved to awaken. Lab work on the molecule has been going on for almost a decade. In the first human trials, conducted in 2023, researchers found that application of PP405 as a topical medicine onto the scalp at bedtime for a week produced promising results. Although cautious with actual data, the UCLA researchers labeled the results “statistically significant.” Most importantly, they believe the treatment will produce full “terminal” hair rather than the peach fuzz variety produced by other contemporary miracle-cure lotions and potions.

 

[OtyMac]

PP405 just happens to be lactate dehydrogenase.

Lowry and Christofk have been working on this since 2017 (https://newsroom.ucla.edu/releases/...-way-to-activate-stem-cells-to-make-hair-grow) so I don't know why the first article claims like it is news.

They are actually rediscovering hormesis which was found out about 60 years ago of different ways to stimulate it.

Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling - Cell Death & Disease

L-lactate was long considered a glycolytic by-product but is now being recognized as a signaling molecule involved in cell survival. In this manuscript, we report the role of L-lactate in stress resistance and cell survival mechanisms using neuroblastoma cells (SH-SY5Y) as well as the C. elegans...

www.nature.com

Until recently, ROS were considered primarily as a hallmark of oxidative stress leading to cellular dysfunction and neurodegeneration15,16. Growing evidence now indicates that ROS may also act as signaling molecules in physiological processes. Indeed, exposure for short periods or low concentrations of ROS contributes to increased lifespan in multiple organisms17,18,19 in a pro-survival mechanism called hormesis or mitohormesis20,21,22.

Here we show that lactate promotes resistance to oxidative stress in both mammalian cells and C. elegans, where pyruvate reproduces the protective effects mediated by lactate. We found that lactate supplementation induces a moderate elevation in ROS levels and the transcription of genes belonging to pro-survival pathways, including the IGF-AKT/PI3K and the endoplasmic reticulum stress pathways.

Our observations suggest that lactate, and to a lesser extent pyruvate, supports resistance to cellular stress through a mild hormetic increase in oxidative stress.

 

[OtyMac]

https://www.sciencedirect.com/science/article/abs/pii/S2468202022000171

Evidence of hormesis and stem cells​

As suggested above, it was learned that hormetic dose responses were commonly reported to occur in a wide range of stem cells, including adipose derived stem cells (ADSCs) [41], apical papilla stem cells (APSCs) [42], bone marrow stem cells (BMSCs) [43], dental pulp stem cells (DPSCs) [44], embryonic stem cells (ESCs) [45], endothelial stem cells (ESCs) [46], induced pluripotent stem cells (IPSCs) [47], muscle/tendon stem cells [48], neural stem cells [49], and periodontal ligament stem cells

 

[Castent]

PP405 just happens to be lactate dehydrogenase.

...

At a minimum this needs clarification, since it's not literally true. PP405 is a small molecule. Enzymes (proteins) such as lactate dehydrogenase are very large molecules.

Per Wikipedia: "Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvate to lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one molecule to another."

From Perlage Pharmaceuticals: "PP405 is a non-invasive, topical small molecule designed to inhibit the mitochondrial pyruvate carrier (MPC) to reactivate dormant hair follicle stem cells and restart hair growth, according to the company."

Of MPCs, Wiki says "This protein is involved in transport of pyruvate across the inner membrane of mitochondria in preparation for the pyruvate dehydrogenase reaction."

This is not my field, so I may be off base. But isn't this implying that PP405 is inhibiting the "pyruvate dehydrogenase reaction"?

[Edit: Apparently this leads to upregulation of LDH: "PP405 is a potent topical mitochondrial pyruvate carrier (MPC) inhibitor that acts on the cellular metabolic pathway to upregulate lactate dehydrogenase (LDH), which stem cells are particularly sensitive to, resulting in their activation and hair growth." [R]]

In any case, is PP405 available as a research chemical yet? The clinical trials are suggesting a reasonable level of safety.

 

[NathanN23]

This sounds like an exciting development in hair loss research! If PP405 can truly awaken dormant follicle stem cells and promote the growth of full terminal hair, it could be a game-changer for those struggling with hair loss. While it’s still early, the fact that initial human trials showed statistically significant results is promising.

That said, we’ve seen plenty of so-called breakthroughs before, and not all of them have lived up to the hype. It’ll be interesting to see how PP405 performs in larger clinical trials and whether it becomes an accessible treatment option.

In the meantime, if you’re looking for proven options to combat hair loss, a free consultation could help you explore the best solutions available today. Check out the link in my signature to learn more!

Nathan