Translating Skin Microbiome Research into Clinical Products
Posted 25th January 2017 by Jane Williams
Collaboration between academia and industry
It has been demonstrated many times in the past that academia and industry, working in tandem, can achieve results to their mutual benefit much faster than when they work in isolation. However, one critical challenge for academic researchers is finding the right partner to commercialise their technology.
During our meetings, Dr. Richard Gallo was eager to see his discoveries lead to more focused and effective treatments for the millions of individuals suffering from serious cutaneous conditions. After discussing the therapeutic potential of selectively modifying the skin, MatriSys Bioscience Inc. was established. Dr. Gallo is head of the Scientific Advisory Board and one of the co-founders of the company.
Bacterial products with antimicrobial properties
Evidence is mounting that beneficial skin bacteria defend their environment by producing antimicrobial peptides that affect the growth of their microbial neighbours. Imbalance of the microbiome and innate immune system is common and contributes to disease severity in many skin conditions.
Atopic dermatitis is a chronic, relapsing, inflammatory disease that is characterised by abnormalities in both skin barrier and immune response. The resulting dry skin, eczematous lesions, and intense itch are treated with combinations of steroids and antibiotics. Compared to healthy individuals, subjects with atopic dermatitis display a lower bacterial diversity that translates in a decreased capability to express certain anti-microbial peptides (AMPs), and an inability to resist colonisation by pathogens such as Staphylococcus aureus. S. aureus can cause diseases ranging from minor impetigo and scalded skin syndrome, to life-threatening septicaemia.
The Coagulase Negative Staphylococcus (CoNS) strains Staphylococcus epidermidis and Staphylococcus hominis are long term residents of the skin. Research at UCSD and other labs has shed light on the molecular mechanisms of communication between resident bacteria on the skin surface and the human cells under the skin surface. S. epidermidis produces antimicrobial molecules that specifically kill members of other bacterial species, including Staphylococcus aureus. In fact, S. epidermidis not only makes antimicrobials, but it also directs human skin cells to produce their own natural antimicrobial peptides.
Gallo’s lab isolated a strain from S. hominis (A9) that secretes novel lantibiotics with specific and potent anti-S. aureus activity. Sh-A9 lantibiotics are commonly found on healthy skin and synergise with the host human AMPs. Promising clinical trials, using an earlier topical formulation of live antimicrobial CoNS in atopic dermatitis patients, found that S. aureus colonisation is dramatically decreased and skin inflammation improved without inflicting severe damage to other beneficial commensal bacteria, and without eliciting toxicity, as this bacterium is a major commensal of normal skin.
The natural re-balance of the skin microbiome achieved with live bacteria therapies shows great therapeutic potential. It is a dramatic improvement over broad-spectrum antibiotics that not only kill pathogenic bacteria, but also destroy the normal skin microflora by friendly fire.
Bringing microbiome based therapies to market
Because the skin microbiome is a novel R&D area, taking microbiome based therapies to market presents a number of several unique challenges for the development of live bacteria therapeutics, compared to traditional biotherapeutics or small molecule drugs. For example, selection of CoNS bacterial strains has to be based on their antimicrobial activity because bacterial species identity doesn’t predict antimicrobial function. Therefore, screening for anti-bacterial effects becomes essential to discover additional beneficial strains.
Considerable attention has to be given to the formulation of live bacterial therapeutics. It is well known that microorganisms survive well when freeze-dried and can be easily rehydrated after prolonged periods of time in storage. MatriSys Bio is currently evaluating this issue, including freeze drying and lyophilisation of the bacteria to achieve two year stability and product efficacy.
Although no clinical toxicity is expected due to the fact that CoNS are normal residents of healthy skin, additional considerations should be paid to the design of non-clinical toxicology studies. Preclinical animal models of human diseases are usually the test for evaluating the effects of novel therapeutic strategies. However, animal models may be of limited use in the development of live bacteria therapeutics, considering that the human microbiome differs significantly from animal microbiomes.
Despite the challenges, the skin microbiome offers unprecedented clinical benefits for a wide range of unmet skin conditions, and represents a unique opportunity for commercial development.
Gilbert-André Keller is the VP of Preclinical Sciences at MatriSys BioScience. Dr. Keller has 25 years of research and development experience in life science industry, and has authored numerous peer-reviewed papers in the fields of pharmacology, oncology, vascular biology and cell biology.
To hear more about bacterial products with antimicrobial properties, watch Richard Gallo’s presentation online.
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