Topical application of heterologous protein-expressing Staphylococcus epidermidis for potential therapeutic treatment of skin diseases

Period of Performance: 08/15/2016 - 07/31/2017

$150K

Phase 1 STTR

Recipient Firm

Azitra, Inc.
NEW HAVEN, CT 06511
Principal Investigator
Principal Investigator

Abstract

PROJECT SUMMARYCurrent treatment options for a number of skin diseases generally aim for symptomatic relief andfail to address underlying pathophysiological changes leading to skin disease. In the case ofgenetic mutations that cause loss of function mutations, supplementation of the missing proteinis a viable approach to treatment. However, delivery of functional protein to the targetkeratinocytes presents a significant challenge; moreover, the cost of protein production andpurification 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, adherence, and convenience.Azitra is a preclinical company focused on microbiome-based therapeutics. We are developing aplatform that consists of an engineered S. epidermidis that is able to establish residence onhuman skin and secrete therapeutic protein in situ. An ointment with an inoculum of such bacteriacould be infrequently applied to skin, providing constant, low-cost, convenient delivery oftherapeutic protein. Natural properties of S. epidermidis also include secretion of antimicrobialpeptides against S. aureus and stimulation of regulatory T-cells, making S. epidermidis an idealsecretion platform.The proposed Phase I research plan will focus on proof-of-concept studies to determine thespatio-temporal growth characteristics of our S. epidermidis production and delivery system (Aim1) and to characterize the spatio-temporal dynamics of sGFP that secreted by S. epidermidis ina skin equivalent model (Aim 2). In the next phase (Phase II) following this STTR Phase I project.The application of this platform will be tested with filaggrin secreted by S. epidermidis in pre-clinical models of atopic dermatitis.