Summary
AZX100 from Capstone Therapeutics is a cell-permeable peptide meant to mimic HSP20 and its ability to relax smooth muscle actin, a feature of myofibroblasts in wounds. Keloids form because of a hyper-responsive positive loop of TGFbeta expression. A lack of ability to limit this loop creates a hyper-cellular tissue with high cell/matrix turnover. Tension has been implicated as a factor in myofibroblast physiology and phenotype. The question will be whether release of tension in these cells will be sufficient to advance the process beyond the myofibroblast toward stable repair.
Analysis
One in vitro study (Chipev et. al, BMC Dermatol. 2:13, 2002) on keloid fibroblasts suggests that release of tension may be able to abrogate the positive TGFbeta loop that lies at the heart of keloid formation. It appears that a key for positive resolution will also be the advance of fibroblast character to a more stable phenotype, i.e. one that favors matrix deposition. Although CTGF, a factor associated with granulation resolution, repair and fibrosis, i.e., stabilizing matrix deposition, is naturally elevated by TGFbeta, CTGF has been observed in the expanding (new) area of the keloid. It will be of interest to see if AZX100 can release tension in the tissue effectively enough to reduce cellularity and whether that will be sufficient to shift the balance in favor of repair. Also, keep in mind there is little additional evidence for the connection of tension and significant biological effect both in vivo and in these genetically predisposed patients.
