Novel Small Molecule Targeting STAT Proteins for the Management of Atopic Dermatitis

Project Summary Atopic dermatitis AD atopic eczema is a chronic inflammatory disease resulting in itchy inflamed swollen skin that is easily susceptible to infection It is estimated by the National Eczema association that there are currently million people affected and at least million of them have moderate to severe disease The current standard of care largely comprises of a multipronged approach involving skin care elimination of allergic triggers and immune suppressive strategies including the use of steroids antihistamines or topical immunommodulators TIMs While these therapies can help partly manage the disease undesirable side effects are seen upon chronic usage Thus given the significant public health burden imposed on the society and the lack of effective treatments there is an unmet need for novel targeted therapeutics that can help manage symptoms and improve the quality of life for AD patients Fannin Partners LLC is an early stage life sciences development group focused on commercializing innovation developed in the Texas Medical Center institutions Led by an experienced team of managers with diverse business backgrounds commercialization experience and strong entrepreneurial knowhow Fannin Partners works with promising life science innovators to help develop and commercialize promising therapeutic technologies for clinical adoption The basic research conducted by Drs John McMurray and David Corry directly led to this innovation Our lead molecule PM I is a small molecule cell permeable and phosphatase stable phosphopeptide mimetic that targets the SH domain of STAT and prevents recruitment to IL R and the subsequent transcriptional activity leading to the atopic dermatitis phenotype The focus of this proposal is to accomplish key milestones that will transition this technology for commercialization for the atopic dermatitis market by conducting in vitro and in vivo proof of concept study The project is organized into two measureable Specific Aims Characterization of STAT phosphorylation and skin barrier gene expression in human keratinocytes in the presence of PM I Keratinocytes play a critical role in AD pathogenesis They show upregulated STAT phosphorylation upon IL and IL stimulation Phosphorylated STAT then down regulates the level of loricrin and ivolucrin two proteins important for skin barrier formation and integrity Our previous studies in asthma have demonstrated that PM I is able to reduce STAT phosphorylation in lung epithelial cells data not shown here we are going to test if PM I also reduces STAT phosphorylation in keratinocytes and subsequent down regulation of LOR and IVL expression To study the efficacy of PM I in atopic dermatitis management Specific Aim A To determine PM I formulation for animal study months This aim is going to determine the best performing topical formulation for PM I in treating atopic dermatitis for the following efficacy study in mouse models Drug solubility stability and in vitro skin permeation will be studied Specific Aim B To study the efficacy of PM I in atopic dermatitis animal models months With the formulation obtained from Aim A we will employ atopic dermatitis mouse model to study the efficacy of PM I in this aim AD clinical score will be used to evaluate the symptoms of mice with or without PM I treatment In addition histology serum cytokines and IgE level and STAT phosphorylation and skin barrier gene expression in keratinocytes will be examined These studies will help to prove the function of PM I in atopic dermatitis on both the symptomatic and molecular level Project Narrative Atopic dermatitis is a chronic inflammatory disease of the skin that is characterized by allergic dermal inflammation resulting in swelling and intense pruritus It is estimated that there are currently million people affected in the US and at least million of them have moderate to severe disease without effective treatment A scientific team from the MD Anderson Cancer Center Dr John McMurray and Baylor College of Medicine Dr David Corry has discovered a new drug that can block a signaling pathway recently shown to be an important component in several mice models of atopic dermatitis Fannin Partners led by a management team experienced in biomedical commercialization in collaboration with Dr McMurray and Dr Corry proposes to further develop and commercialize the new drug molecule for eventual clinical usage in atopic dermatitis