Commensal Skin Bacterium Engineered to Deliver Key Protein with
Potential to Treat Rare Genetic Skin Disorder, Netherton Syndrome
FARMINGTON, Conn.–(BUSINESS WIRE)–Researchers from Azitra,
Inc., in collaboration with independent, nonprofit biomedical
research institution The
Jackson Laboratory (JAX), 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 as AZT-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-02
offers 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 by Travis 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, 2019 in Hannover, Germany.
S. epidermidis is 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 of S. 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.”
NS is 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. LEKTI’s
function is to inhibit protease enzymes in the skin that facilitate the
shedding of skin cells. When LEKTI is absent (in severe cases) or has
reduced activity (due to a more minor genetic defect), excess shedding
occurs, and the skin is sensitive, open, red, and scaly. This is
accompanied by a disruption of the skin’s barrier function, dehydration,
and potential exposure to allergens, infectious agents, toxic chemicals
and other environmental hazards. Complications of NS are frequent, and
newborns with the disorder are at risk of becoming dehydrated and
developing skin infections or sepsis, which can be threatening. There
are currently few treatment options for NS.
“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-02 for 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.”
This study was supported by a grant from the National Institutes of
Health (National Institute of Allergy and Infectious Diseases and
National Institute of Arthritis and Musculoskeletal and Skin Diseases),
the National Science Foundation, and Breakout Labs.
About Azitra
Azitra, Inc. is a clinical-stage biotechnology company combining the
power of the microbiome with cutting-edge genetic engineering to treat
skin disease. The company was founded in 2014 by scientists from Yale
University and works with world-leading scientists in dermatology,
microbiology, and genetic engineering to advance its consumer health and
pharmaceutical programs to treat atopic dermatitis, dry skin, cancer
therapy associated skin rashes and targeted orphan indications. For more
information visit http://www.azitrainc.com.
About The Jackson Laboratory
The Jackson Laboratory (www.jax.org)
is an independent, nonprofit biomedical research institution with more
than 2,200 employees. With a mammalian genetics institute as its
headquarters campus in Bar Harbor, Maine, it has a genomic medicine
institute in Farmington, Conn. and production facilities in Sacramento,
Calif., and Ellsworth, Maine. Its mission is to discover precise genomic
solutions for disease and empower the global biomedical community in the
shared quest to improve human health. For more information, please visit www.jax.org.
Contacts
Michelle Linn
Bioscribe, Inc.
774-696-3803
michelle@bioscribe.com