Efficacy and Safety Study of p144 to Treat Skin Fibrosis in Systemic Sclerosis
Status:
Completed
Trial end date:
2010-09-01
Target enrollment:
Participant gender:
Summary
Transforming growth factor-beta 1 (TGF-β1) is consistently over expressed in most fibrotic
diseases and displays a variety of profibrotic effects in fibroblasts. Activation of TGF-β
receptors induces the activation of several kinase signalling cascades leading to the
phosphorylation of SMAD proteins as well as to the activation of SMAD-independent kinases
that collectively activate ECM synthesis and fibroblast growth and differentiation into
myofibroblasts. TGF-β1 is one of the main mediators in the fibrotic process, associated to
both scarring and a long list of pathologies related to chronic inflammation and which affect
all type of organs and tissues. An increase in TGF-β1 mRNA and protein levels has been
described in these processes. Peptide 144 (P144) is the acetic salt of a 14mer peptide from
human TGF-β1 type III receptor (betaglycan). P144 TGF-β1-inhibitor has been specifically
designed to block the interaction between TGF-β1 and TGF-β1 type III receptor, thus blocking
its biological effects. P144 has shown significant antifibrotic activity in mice receiving
repeated subcutaneous injections of bleomycin, a widely accepted animal model of human
scleroderma, and could contribute to the development. The purpose of this study is to asses
the efficacy and safety of topical application of P144 in the treatment of skin fibrosis in
patients with systemic sclerosis.