Category Archives: Lactate

Heather Christofk, Lactate, Pelage Pharmaceuticals, PP405, William Lowry

Pelage Pharmaceuticals Raises $16.75 million and Phase 2 Trials to Begin in 2024

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Pelage Pharmaceuticals
Pelage Pharmaceuticals Logo.

I previously wrote about Pelage Pharmaceuticals in my 2019 post  related to the research of its President and co-founder Dr. William Lowry. The other co-founders are Dr. Heather Christofk and Michael Jung. I also covered the findings of Dr. Lowry and Dr. Christofk’s UCLA team in a 2017 post.

These UCLA researchers discovered two topical compounds (RCGD423) and (UK5099) that regrew hair in mice via different mechanisms. Both drugs involve an increase in lactate production. This in turn activates hair follicle stem cells and leads to increased and quicker hair growth.

Dr. Lowry’s patent can be found here. Patent and technology rights to both topical drugs have been exclusively licensed to Pelage Pharmaceuticals by UCLA.

Update: March 9, 2024

Earlier today, Pelage Pharmaceuticals gave a positive update on its novel small molecule PP405. Full summary can be read here. In Phase 1 clinical trials, PP405 reactivated dormant hair follicle stem cells and triggered hair growth. The company’s presentation was made by Dr. Christina Weng and titled: “Inhibition of pyruvate oxidation activates human hair follicle stem cells ex vivo”. Pelage will begin its multi-center Phase 2a trial of PP405 in mid-2024. It will recruit both men and women with androgenetic alopecia.

Their description of this unique hair growth molecule is as follows:

“PP405 is a potent topical mitochondrial pyruvate carrier (MPC) inhibitor that acts on the cellular metabolic pathway to upregulate lactate dehydrogenase (LDH).”

Stem cells are particularly sensitive to LDH, so this results in their activation and subsequent hair growth. PP405 demonstrates a statistically significant increase in Ki67 signaling in the hair follicle bulge. Ki67 is a well-established marker of stem cell proliferation.

Pelage Pharmaceuticals Raises $16.75 Million and Phase 2 Trials to Begin in 2024

February 27. 2024

Great new update (h/t “YoYo”). Pelage Pharmaceuticals has raised $16.75 million in Series A Financing. More importantly, they will begin Phase 2 Clinical Trials for PP405 in mid-2024.

Phase I clinical data met primary safety endpoints. And they confirm that their was statistically significant stem cell activation in hair follicles after just one week of treatment with PP405.

Per CEO Daniel Gil, Ph.D.:

“Our scientific co-founders have uncovered a unique biological mechanism with the potential to reactivate hair growth in people with alopecia.”

The company will present translational data at the American Academy of Dermatology meeting in March 2024.

February 17, 2024

Earlier today, reader “Ben” made an very interesting discovery on Pelage Pharmaceuticals’ website. The following sentence at the bottom:

“Early Phase I clinical data shows statistically significant stem cell activation in the hair follicles after one week of treatment with PP405.”

This is super news. So their trials have started. I wonder if PP405 is RCGD423 or UK5099? Their website homepage describes PP405 as:

“A novel, non-invasive, topical small molecule drug platform that activates stem cells in the hair follicles directly to stimulate robust hair growth. By targeting an intrinsic metabolic switch in hair follicles, Pelage’s platform is suitable for all genders, skin types, and hair types.”

In other recent news, Pelage appointed Dr. Qing Yu Christina Weng as Chief Medical Officer.

RCGD423

RCGD423 activates the JAK-STAT signaling pathway, which in turn leads to an increase in lactate production. This extra lactate activates hair follicle stem cells and results in quicker hair growth.

UK5099

UK5099, blocks pyruvate (a glucose metabolite) from entering cell mitochondria. This also results in an increase in lactate production in the hair follicle stem cells, and therefore accelerates hair growth.

JAK-STAT, Lactate, RCGD423, UK5099

UCLA vs USC in the Hair Loss World

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University of California Los Angeles (UCLA) and University of Southern California (USC) are both based in Los Angeles, California in the USA. They have one of the most intense and historic rivalries in American college sports, especially in American football. The two campuses are separated by just 12 miles. In an amazing coincidence, the two most important hair loss research related discoveries in the world this month came out of these very two universities.

UCLA scientists find two new ways to activate hair follicle stem cells

For our purposes, the UCLA findings (published just today) seem to have the greatest significance. Scientists (led by Heather Christofk and William Lowry) have found two drugs that activate hair follicle stem cells in mice. Interestingly, both drugs are topical, and one (RCGD423) involves activating the JAK-STAT signaling pathway. No idea if this drug is connected to JAK inhibitors in any way, but that acronym keeps coming up regularly these days.

Both drugs involve increasing lactate production. Apparently, lactate production is strongly connected to hair follicle stem cell activation and hair cycling. In their initial research, the UCLA scientists blocked lactate production genetically in mice and found that this prevented hair follicle stem cell activation. Thereafter, they found that increasing lactate production genetically in mice accelerated hair follicle stem cell activation and increased the hair cycle.

RCGD423

The first drug, RCGD423, activates the JAK-STAT signaling pathway, which in turn leads to an increase in the production of lactate. This then activates hair follicle stem cells and also leads to quicker hair growth. UCLA holds the original patent for RCGD423, related to its ability to rejuvenate cartilage, and has filed a provisional patent for its use for hair growth purposes.

UK5099

The second drug, UK5099, blocks pyruvate (a glucose metabolite) from entering cell mitochondria. Interestingly, this forces an increase in the production of lactate in the hair follicle stem cells and therefore accelerates hair growth. UCLA has filed a provisional patent for using UK5099 for hair growth purposes.

Perhaps the most interesting quote from the earlier linked article summarizing these findings is: “I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general“. On this blog, I have covered the connection between fat cells (adipose tissue) and hair growth numerous times due to significant recent research in that area. So I am not surprised at all that metabolism is also important when it comes to hair growth.

It is, however, surprising that hair loss research has uncovered so many new distinct pathways and mechanisms in the past few years. All of these are unrelated to the tried and tested method of targeting dihydrotestosterone (DHT) reduction. This is great news, since we already know that even close to 100 percent reduction in DHT will not bring back long-lost hair for most people, plus often comes with side effects.

USC scientists restore hair generation in defunct adult cells

A team of scientists from USC (led by Dr. Mingxing Lei, with collaboration from others in China and the UK) have managed to restore hair regeneration properties in adult mice cells that had stopped growing hair. A non-scientist friendlier summary of this work can be found here. One of the co-authors of this paper is Dr. Cheng-Ming Chuong, who I covered on this blog before.

Using intensive video analysis and documentation, bioinformatics, and molecular screenings, the scientists figured out a:

Molecular “how to” guide for driving individual skin cells to self-organize into organoids that can produce hair.

Also:

In the future, this work can inspire a strategy for stimulating hair growth in patients with conditions ranging from alopecia to baldness.

Very unlikely to come to fruition anytime soon of course, but considering that some of the research collaborators are from China… perhaps things may move faster than I am guessing if they could shift their research and potential clinical trials to that country?