Tag Archives: skin disease

Atopic Dermatitis, Bugs, and Itching

The skin barrier in the epidermis is constantly exposed to microbes and their products. The role of microbes in itch generation was previously unstudied. Deng et al (2023) find that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch.

When the scientists injected MRSA, a type of S. aureus, under the skin of mice, as expected, the mice itched so much that they damaged their skin. But the authors claim to have measured no inflammation associated with the injection. This provides evidence that inflammation is not required for itch to occur.

Instead, research has found that when S. aureus invades the skin, it releases 10 different enzymes, or proteases. One of them, called V8, binds to a protein on nerve cells called proteinase-activated receptor 1, or PAR1. Activation of PAR1 likely starts a chain reaction from the skin neurons, to the spinal cord, and to the brain, which then triggers the urge to itch. In the mouse model used by Deng et al, the itching stopped when researchers used Vorapaxar, a drug that blocks the PAR1 receptor. This may not be the only mechanism by which itching occurs, but this is an important new discovery and gives us much insight into the some of the mechanisms underlying pruritis.

From Deng et al (2023)

As Ogonowska et al (2023) have described, Staphylococcus aureus massively colonizes the skin of patients with atopic dermatitis (AD), and the frequency of detection of multidrug-resistant S. aureus (MRSA) in AD patients is higher than the healthy population, which makes treatment much more difficult. 

There’s hope though, and that hope involves using simple, topically applied symbiotic bacteria that are safe and natural to the skin. One set of bacteria are the nitrifying bacteria (Nitrosomonas, Nitrospira, and Nitrobacter), used in NeoGenesis MB-1. The MB-1 product has been on the market since 2015 and is multifunctional – benefiting a number of skin conditions, including acne. As one mechanism of action, Maguire and McGee (2023) hypothesize the MB-1 acts to destroy pro-inflammatory bacteriophage (viruses) associated with acne through a natural CRISPR mechanism in the probiotic bacteria.

These type of nitrifying bacteria in MB-1 have also been found to reduce pruritis and inflammation in humans with atopic dermatitis. Additionally, NeoGenesis is currently testing our second probiotic product that incorporates Bacillus subtilis and Lactobacilli. The bacterium B. subtilis has been found to reduce the S. aureus when topically applied, and Lactobacilli have been found to do the same while reducing the symptoms of AD.

NeoGenesis will have two probiotic products that will be used together in a topical application to renormalize the skin’s microbiome in AD, reduce pruritis, and restore barrier function. Stay tuned.

The Reductionist Pharma Mindset in Start-Up Skincare Companies – Purveyors of Magic Bullets

The recent spate of start-up skincare companies featuring technologies that rely on one one magical ingredient belie the complexities of the skin’s physiology – When will they ever learn about “Systems Therapeutics for Physiological Renormalization”?

Some recent examples of magic bullets being funded by venture capital and brought to the market by their marketing puppets include: the long-available and widely used ingredient called, phytosphingosine; a peptide du jour called OS-01 Peptide; another peptide du jour with the tradename, LIPOXERASE. I could go on, but these are a few examples that popped up on my radar over the weekend. Let’s be clear, the mindset of these private equity funded skin care companies is to develop skin care products in the same manner as drug companies. That mindset is reductionist, meaning that they feature one ingredient as a “cure all.” But making drugs that cure a disease is a bad business model – if it’s cured, the customer goes away and money is lost. The reductionist strategy is why most drugs don’t work, and most have serious negative side-effects. I wrote a book about this. Pharma knows it. Often the key is to develop one ingredient for which a patent can be attained. It doesn’t matter if the patented ingredient really works, it just matters that a patent is in place. Once the patent is granted, no one else can use the ingredient for about 15-20 years. This makes for great marketing hype in the USA. A new patented ingredient will spread like wild fire through the corporate media circles, and having heard the corporate media hype thousands of times over, many will believe the nonsense. These companies will make money, because with private equity behind them, they’ve got the money to hire the Mad Men. Private equity is a huge negative for healthcare. It doesn’t matter that the new patented or “patent-pending” (anyone can say this) product doesn’t work well, media hype will say that it does and people will buy it. Private equity makes money, your skin will whither.

So when will these people learn about “Systems Therapeutics for Physiological Renormalization“? The skin has a very complex physiology. And when you have a skin disease, the changes in physiology are complex. The disease is not about one pathway in the skin changing, and then using one ingredient to fix the pathway. Rather, disease is complex and involves many pathways, and a systems therapeutic that targets multiple pathways underlying the disease is required to significantly ameliorate the disease. That means many molecule types are delivered to the skin to renormalize the physiology, affecting all or many of the pathways underlying the disease, and to bring the skin back to a non-diseased state. This is the approach we use at NeoGenesis, the skincare company that I co-founded. We use a multitude of molecules, most of which are skin-identical, to renormalize the skin’s physiology. Those skin identical ingredients include the S2RM molecules – a collection of many molecule types that are released from adult stem cells derived from human skin. These molecules are an example of endogenous skin identical ingredients, because they are molecules produced by cells in the skin. We also use exogenous skin identical ingredients, such as Vitamin C, A, and E and essential fatty acids, that are derived from a healthy diet. These are all skin identical ingredients because they are normally found in the skin and man evolved to naturally use these ingredients, whether they are made in the skin or acquired through diet. Choosing a myriad of healthy ingredients with which man co-evolved is how I formulate our products at NeoGenesis. It’s not about one magical ingredient, it’s about a collection of healthy ingredients.