dNovo: De Novo Hair Regeneration

A new biotech startup named dNovo is all over the news this week when it comes to the hair loss world. They have already grown reprogrammed human hair on mice.

dNovo stem cell hair loss cure
Stem cell hair loss cure from dNovo. Proven in mice so far.

I am no longer keen to cover startup hair loss cure related companies that have yet to even commence pre-clinical trials. In all past such cases, we have always been left with major disappointment. Such companies waste years of our time before ending up in situations such as the below:

  • Fail or see minimal results during Phase 1, Phase 2 or Phase 3 clinical trials (e.g., Follicum). Then they discontinue.
  • Cannot raise sufficient funds at some point very late in the process. (e.g., Riken/Tsuji and Intercytex/Aderans).
  • Close down their hair loss program abruptly with no clear explanation (e.g., Aclaris). In many cases, despite decent hair growth results.
  • Keep announcing minor new developments even ten plus years after inception, with no end in sight. e.g., Follica just released a poster.
  • Get involved in licensing and other partnership disputes (e.g., Shiseido/Replicel).

I increasingly feel that most new companies are all money-making schemes to raise investor funds or boost share prices. But the hope for someone legitimate never ends (at least not till I finally shave my head).

dNovo: Hair Growth with Stem Cells

However, for the past three days, dNovo has been in the news every day and several readers commented and e-mailed about the company. “De novo” stands for “anew” or “from the beginning”. i.e., brand new hair follicle formation in this case. Note that there is another company named “denovo hair” (but their site suggests it is no longer in business).

The initial detailed article on dNovo was published in MIT Technology Review. Then came Fortune. Followed by BoingBoing. Today, I finally gave in after Slashdot also got in on the game. The comments underneath their article are funny.

I am covering dNovo despite major reservations. Assuming they even succeed in humans, I do not think that dNovo’s hair cell regeneration product can come to market before 2030. And Stemson will likely beat them to the game.

dNovo Cell Reprogramming Process

dNovos’s lab-grown hair process is outlined on their site in five steps:

  1. Collect human hair cells at their facility.
  2. Add proprietary reprogramming factors.
  3. General hair producing cells.
  4. Seed these cells into the balding recipient’s scalp.
  5. See visible hair growth in 1-3 months post implantation.

As of second quarter 2021, dNovo had successfully developed the reprogramming system to generate human dermal papilla cells (patent pending). These reprogrammed dermal papilla cells perform biochemically as expected of human dermal papilla cells.

At the end of 2020, the company successfully transplanted reprogrammed human hair stem cells onto mice. These then turned into actual human hair (image at the top of this post).

Dr. Ernesto Lujan

dNovo was founded in 2018 by Stanford University educated biologist Dr. Ernesto Lujan. He has a PhD in genetics, and has many other accomplishments per his bio on YCombinator. dNovo’s team consist of PhDs and MDs trained at Stanford, Harvard, and Caltech.

Dr. Lujan was a co-author of a 2012 paper in which his team  converted mouse skin cells into cells that become the three main parts of the nervous system. So it seems like he has been interested in this type of cell reprogramming work for at least ten years.

I love this quote on YCombinator:

“After hair, we envision using our cellular reprogramming technique to make any cell, any tissue or any organ on demand to replace what is lost as we age.”

Per Dr. Lujan (in Fortune magazine):

“We are currently in the preclinical stage of development. We have shown the results in laboratory mice and are very excited with those. We hope to eventually demonstrate the efficacy in human trials and make our product commercially available, but at the moment we are in the early stages of the whole process.”

Oral Minoxidil to Treat Hair Loss

Since I first wrote this post, there have been a number of new oral Minoxidil and hair growth related studies and updates. Please consult your doctor or dermatologist before taking oral or sublingual Minoxidil.

Sublingual versus Oral Minoxidil

Oral Minoxidil Generic 5 mg.
Oral Minoxidil 5 mg.

The biggest new update was initiated yesterday by “Nik” on our Discord group. He mentioned how sublingual Minoxidil (3 mg/day in one go) was superior to oral Minoxidil in growing hair amongst his friends. Make sure to read my past post on Minoxidil as a sublingual tablet.

He then linked to this 2020 report on 64 patients where the dose was only 0.45 mg/day. The author is Dr. Rodney Sinclair of Australia, who I cover in detail at the bottom of this post. I posted about this on Twitter, and Dr. Corralo from Spain responded with an interesting comment.

Upon further research, I also found this newer August 2021 report from Dr. Sinclair. It entails a Phase 1B clinical trial, which is very encouraging news. Detailed summary from October 2021 can be read here. The interest in oral Minoxidil for hair growth has really taken of during the past few years. Online anecdotes indicate superiority over topical Minoxidil, but I am not yet 100 percent certain.

“Almost 67% of patients who received the 4.05 mg dose experienced improvements in frontal and vertex hair density. In the 0.45 mg dose group, phototrichograms showed a mean increase in terminal hair count/cm2 of 4 for the frontal and 9 for the vertex scalp. Treatment with the 1.35 mg dose resulted in a mean increased terminal hair count/cm2 of 10 and 26. The 4.05 mg dose led to a mean increase terminal hair count/cm2 of 38 for the frontal and 88 for the vertex scalp.

According to Dr. Mirmirani’s succinct summary at the bottom of that page:

“The authors suggest that sublingual Minoxidil (SM) may have better bioavailability and fewer hemodynamic effects by avoiding first-pass liver metabolism. Will SM be a game changer? Although the data in this study are positive, it will take more to convince me that it is significantly better than oral Minoxidil (OM). Very few of my patients on low-dose OM for hair loss discontinue the medication due to side-effects. The other consideration is cost. OM it is an inexpensive, generic drug, that is covered by medical benefits.”

New Studies

Update: October 2021 — New study finds that low-dose oral minoxidil increases hair density and thickness.

Update: August 2021 — A review of low dose oral Minoxidil treatment for hair loss.

Update: February 2021 — Safety of low-dose oral minoxidil (LDOM) for hair loss in 1404 patients. Multicenter study. The most frequent adverse side effect was hypertrichosis.

Oral Minoxidil Hair Growth
Oral Minoxidil Hair Growth Before and After. Source: JAAD.

Since I first wrote this post on oral Minoxidil several years ago, a number of major new developments have occurred.

An October 2020 study of low-dose 1.25 mg nightly treatment with oral Minoxidil (Loniten) for three months concluded favorable increases in hair growth. More here. This is surprising, considering the low dose utilized relative to other studies. The hair loss patients included males and females of various ethnicities. Further treatment with 2.5 mg dosing was also analyzed.

In September 2020, a Thai study found good results for men taking oral Minox 5mg daily. In July 2020, a review of 16 studies encompassing 622 patients concluded that oral Minoxidil is an effective and well-tolerated hair loss treatment. However, more statistical data is still needed. Also see this June 2020 article that concludes low-dose 1.25 mg/day

In August 2019, Spanish researchers published positive findings on low-dose 5 mg per day oral Minoxidil. One of the results from this study can be seen in the above before and after hair growth photo. It was sent to me by Dr. Sergio Vañó.

Oral Minoxidil for Hair Loss

For many years, I have heard that oral Minoxidil results in even more hair growth compared to the topical version. This is true for both male and female pattern hair loss (often in combination with Spironolactone for women). However, I always assumed that the side effects from the oral medication would be much worse.

The health related side effects include blood pressure fluctuations, heart rate changes, and potential water retention. However, I was most concerned about the side effect of excess body hair growth from Minoxidil pills turning me into a werewolf. Note: Make sure to read my post on topical Minoxidil and beard growth.

Introduction

I have discussed Minoxidil (brand name Rogaine) many times on this blog in the past. It is one of only two drugs officially approved by the US FDA to treat male pattern hair loss. The other being Finasteride, which targets dihydrotestosterone (DHT) reduction.

Most men use 5% topical Minoxidil foam and apply it to their scalps twice per day. For those who get adverse reactions, dosage is sometimes reduced to once per day. Women tend to use the 2% topical formulation to regrow thinning hair. Very few people use oral Minoxidil to treat male androgenetic alopecia or female pattern hair loss.

Unbeknownst to many, Minoxidil was originally approved in 1979 as an oral medication (brand name “Loniten”) to treat hypertension (high blood pressure). It was only approved for treating hair loss in men in 1988 as a topical medication.

A women’s version was approved in 1991. To this day, it is not entirely clear as to how Minoxidil works in promoting hair growth, with a number of theories out there, implying the likely involvement of multiple mechanisms. These include agonistic affects on adenosine-triphosphate (ATP)-sensitive potassium channels; prostaglandin stimulation in the dermal papillae; and anti-androgenic properties.

Low-Dose Oral Minoxidil for Hair Loss

Several years ago, I read a very lengthy and thoughtful comment by Thai hair transplant surgeon Dr. Damkerng Pathomvanich. He outlined why he prescribes oral Minoxidil to a select few of his patients   Low-dose oral Minoxidil (LDOM) for hair loss in select patients can be very effective. Update: In October 2020, Dr. Ratchathorn Panchaprateep from Thailand also released positive findings in relation to this drug.

According to Dr. Path (as well as per other physicians that had given him feedback), 5 mg per day was an ideal dosage that did not change patient blood pressure readings significantly. Some physicians even recommend trying 2.5 mg per day. In fact doses as low as 0.25 mg to 1.25 mg per day have results in hair growth in some patients.

However, some western publications and websites recommend a lower dosage (see links in some of the comments to this post). Image below shows generic 5 mg Minoxidil tablets from Thailand. Please do not try to buy this online as it can be dangerous.

Side effects are still possible at low doses. Dr. Pathomvanich does not prescribe oral Minoxidil to patients who have blood pressure, heart, liver or kidney problems.

Note that according to the official brochure for Loniten, maximum recommended dosage is listed as high as 100 mg per day, which seems crazy. Most patients taking the drug for hypertension do not cross 40 mg per day.

Side Effects

Another major recent news story regarding oral Minoxidil also comes from Spain in August 2019. Apparently, 17 infant children were mistakenly given oral Minoxidil instead of heartburn medication.

Update: December 2020 — Over a year after the medical error, families of some children are complaining that the body hair keeps growing. Also from Spain, a September 2020 study on low-dose oral Minoxidil and hypertrichosis.

Oral Minoxidil Hypertrichosis Body Hair Side Effect.
Oral Minoxidil Excessive Body Hair Increase Side Effect.

The children subsequently developed a condition called “werewolf syndrome” in which large parts of their bodies become covered in hair. This condition is also referred to as hypertrichosis.

Luckily, the body hair will disappear a few months after the children stop taking oral Minoxidil. Above photo is from the video of this shocking news story.

Dr. Sinclair Recommends Oral Minoxidil

I had forgotten about the above till today, when commentator “Billa” posted an interesting link to a new audio interview with Australian Dr. Rodney Sinclair. I have covered this well known hair expert a number of times on this blog in the past.

In this latest interview, one of the things that Dr. Sinclair states is that oral Minoxidil is much more effective than topical Minoxidil when it comes to hair growth. He reaches this conclusion based on some clinical trials that his clinic is currently undertaking. Make sure to also check out my post on Dr. Sinclair’s Hairy Pill.

While the article describing the above interview states that side effects from oral Rogaine were not significant, I did not hear that in the audio interview. I am guessing that this must be true or else they would stop conducting the trials.

Dr. Sinclair has also successfully tested oral Minoxidil and Spironolactone combination treatment in female pattern hair loss patients.

Note that oral Minoxidil is not currently FDA approved for treating hair loss. I do not intend to take the drug, mostly because I do not want to risk getting any more body hair.

Another doctor from Australia recommends oral Minoxidil for hair loss:

Hair loss news blog. Hair cloning for baldness.