Bioengineered skin microbiota for cutaneous mitigation of Netherton Syndrome

Information

  • Research Project
  • 9526200
  • ApplicationId
    9526200
  • Core Project Number
    R43AR073562
  • Full Project Number
    1R43AR073562-01
  • Serial Number
    073562
  • FOA Number
    RFA-AR-18-005
  • Sub Project Id
  • Project Start Date
    8/1/2018 - 6 years ago
  • Project End Date
    7/31/2019 - 5 years ago
  • Program Officer Name
    CIBOTTI, RICARDO
  • Budget Start Date
    8/1/2018 - 6 years ago
  • Budget End Date
    7/31/2019 - 5 years ago
  • Fiscal Year
    2018
  • Support Year
    01
  • Suffix
  • Award Notice Date
    7/30/2018 - 6 years ago
Organizations

Bioengineered skin microbiota for cutaneous mitigation of Netherton Syndrome

PROJECT SUMMARY Current treatment options for many skin diseases?especially rare diseases?fail to address the underlying causative pathophysiologies. In the case of genetic mutations that cause loss of function mutations, supplementing the missing protein is a viable approach to treatment. However, delivery of functional protein to the target keratinocytes presents a significant challenge; moreover, the cost of protein production and purification creates a significant hurdle to developing a commercially viable treatment. Finally, given the natural turnover rate in the skin, constant reapplication of protein would be needed, which compounds issues related to cost of treatment, compliance, and convenience. Azitra is a preclinical company focused on microbiome-based therapeutics. We are developing a platform that consists of an engineered Staphylococcus epidermidis, a common skin species that establishes residence on human skin and secretes therapeutic protein in situ. A preparation of such bacteria could be infrequently applied to skin, providing constant, low-cost, and convenient delivery inoculum of therapeutic protein. Natural properties of S. epidermidis also include secretion of antimicrobial peptides against disease-causing agents like S. aureus and stimulation of regulatory T-cells, making S. epidermidis an ideal secretion platform. This Small Business Innovation and Research (SBIR) project aims to establish proof-of-concept development of an iteration of our drug delivery platform consisting of engineered commensal skin bacterial species for the potential treatment of a rare and severe skin disease, Netherton Syndrome. Importantly, we will demonstrate that S. epidermidis can secrete functional LETKI protein (the protein that is missing in patients with Netherton Syndrome) and that these bacteria can improve phenotypic severity of the disease in a mouse model. The small business concern, Azitra Inc., is currently developing preclinical candidate recombinant bacteria for in situ protein delivery for treating skin diseases. The academic partner, the Jackson Laboratory for Genomic Medicine, is located less than a mile from Azitra and has world-class facilities and subject matter expertise to co-direct experimentation and key analyses, particularly given its resources and expertise in the skin microbiome and mouse models. Together, we will establish that LETKI-secreting skin commensals is a viable, novel, and potent drug delivery method for treating Netherton Syndrome by secreting functional proteins in situ for therapeutic benefit.

IC Name
NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
  • Activity
    R43
  • Administering IC
    AR
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    225000
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    846
  • Ed Inst. Type
  • Funding ICs
    NIAMS:225000\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZAR1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    AZITRA, INC.
  • Organization Department
  • Organization DUNS
    079266596
  • Organization City
    Farmington
  • Organization State
    CT
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    060321913
  • Organization District
    UNITED STATES