Targeting WWP2 for Treating Diseases Characterized by Fibrosis
PATENT STATUS
UK patent application disclosing this invention was filed in June 2019.
OVERVIEW OF TECHNOLOGY ON OFFER
A new therapeutic strategy involving the inhibition of WWP2 expression and/or its activity to treat diseases characterized by pathological inflammation and fibrosis.
BRIEF DESCRIPTION
Tissue fibrosis occurs when the ongoing natural healing process in a tissue is dysregulated, which as a consequence creates damaging extra scar tissue. Although substantial progress has been made in understanding the pathogenesis of excessive tissue fibrosis and fibrotic disorders, there is still no effective (and safe) cure. As fibrosis and resultant organ failure account for at least one third of natural deaths worldwide, management of fibrotic diseases still present an important economic burden for human health. There are several common important fibrotic diseases (atherosclerosis, cirrhosis, scleroderma, pulmonary fibrosis, etc.) and since there are no effective treatments to prevent fibrotic tissue from forming, fibrosis is often considered to be an irreversible process. In the clinic, doctors typically try to slow down the fibrotic progress by anti-inflammatory and immunosuppressive drugs, which however lack specificity and present considerable toxicity. Thus, effective and adverse-side-effect free therapies for fibrotic diseases have not been achieved yet. Many fibrotic diseases share the common feature of disordered and exaggerated deposition of extracellular matrix (ECM) in affected tissues (e.g., kidney, lungs, heart), although the specific aetiology and causative mechanisms might differ across diseases.
In an attempt to overcome these obstacles, scientists from the Cardiovascular and Metabolic Disorders Research Programme at Duke-NUS conducted an array of bioinformatics analyses to identify novel molecular candidates that are linked to fibrosis, and found an E3 ubiquitin ligase called WWP2 to be pivotal in the pro-fibrosis molecular network. With the aid of in vitro loss- and gain-of-function studies, and WWP2 knockout mouse models, our scientists have shown that WWP2 is a key regulator of the extracellular matrix (ECM) accumulation in the diseased heart downstream of TGFβ/SMAD signaling. This pro-fibrotic function of WWP2 was found to be mainly associated with its N-terminal region, which our scientists believe is a novel and druggable therapeutic target with the potential to control fibrosis in pathological cardiac remodelling. In addition, WWP2 was also found to be a key factor augmenting kidney fibrosis. In summary, Duke-NUS scientists identified a novel, specific drug target for treating tissue fibrosis.
POTENTIAL APPLICATIONS
Treatment of pathological inflammation and fibrosis in several organs.
KEY BENEFIT
Targeting a specific molecular candidate (WWP2 protein) for treatment of several pathologies caused by inflammation and fibrosis.
PUBLICATION
Chen et. al. “WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling” Manuscript accepted for publication in Nature Communications.
INVENTOR BIO
Petretto Enrico Giuseppe
CONTACT
Please email us for further enquiries:
cted@duke-nus.edu.sg