On 4/8/19 researchers from Azitra, Inc., in collaboration withindependent, nonprofit biomedical research institutionThe Jackson Laboratory (JAX), announced they have demonstrated the feasibility of engineering a commensal bacterium to deliver a key therapeutic protein to the skin. Azitra will be presenting results from the joint research showing the successful genetic engineering of the common skin bacterium, Staphylococcus epidermidis, to produce high levels of functional LEKTI protein, a protease inhibitor involved in regulating the rate of skin loss. The company has designated the engineered LEKTI-expressing S. epidermidis strain asAZT-02, and the research team, including Julia Oh, Ph.D., a skin microbiome expert at JAX has also shown that engineered S. epidermidis efficiently colonizes skin in both wild type mice and in a mouse model of broken skin. Applied topically, AZT-02offers the prospect for continuous and cost-effective delivery of functional LEKTI to the skin offering the potential to treat the severe genetic skin disease Netherton syndrome(NS).
The new research will be presented on April 10 byTravis Whitfill, MPH, founder and Chief Scientific Officer of Azitra as an oral presentation entitled, “Engineering the Microbiome to Treat Netherton Syndrome, a Rare Skin Disease” at the Keystone Symposia on Skin Health and Disease, held from April 8-11, 2019in Hannover, Germany.
S.epidermidisis a normal constituent of the skin microbiome, and on its own has been shown to help maintain healthy skin by improving the water and lipid content of the skin, decreasing inflammation, promoting tissue repair, and suppressing the levels of undesirable bacteria, including Staphylococcus aureus. Azitra’s core technology combines these characteristics of S. epidermidis with the added ability of delivering therapeutic proteins to the skin. This dual action aims to correct underlying skin defects and address the challenges of dysbiosis to treat complicated skin diseases.
“Azitra has developed a proprietary strain ofS. epidermidis with an aim of using this bacterium as a platform for the treatment of skin diseases,” said Mr. Whitfill.“While this organism has the potential for use on its own to help maintain skin health, we are also developing it to serve as a unique delivery system for the cost-efficient production and topical delivery of important therapeutic proteins. These proteins are targeted to treat serious skin disorders. The work presented today clearly demonstrates the feasibility of this approach for the efficient, topical delivery of LEKTI to the skin. The strain, AZT-02,has the potential to be used as a treatment for Netherton syndrome, which is a rare genetic skin disease with no available treatment options.”
NSis a genetic disorder affecting 1 in 200,000 children,caused by mutations in the SPINK5 gene that is responsible for making the LEKTI (lympho-epithelial Kazal-type related inhibitor) protein.
We have shown with this research that our proprietary strain of S. epidermidis can be engineered for the delivery of therapeutic proteins and can efficiently colonize both healthy and diseased skin,” said Mr. Whitfill. “Azitra is now planning further studies to evaluate the efficacy of AZT-02for the potential treatment of NS. The company is also investigating other indications—such as atopic dermatitis—for additional therapeutic uses with this platform of delivering therapeutic proteins by a commensal skin organism.”