The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe,
Arizona), is a twenty-three-amino-acid peptide that represents a portion of
the receptor-binding domain of the native human thrombin molecule that has
been identified as the binding site for a specific class of receptors on
fibroblasts and other cells. Preclinical studies with this peptide have shown
that it can accelerate tissue repair in both soft and hard tissues by
mechanisms that appear to involve up-regulation of genes that initiate a
cascade of healing events. These events include recruitment and activation of
inflammatory cells, directed migration of cells (chemotaxis), cell
proliferation, elaboration of extra-cellular matrix, and accelerated
revascularization of the healing tissues.
Early preclinical dermal wound-healing studies showed that TP508
accelerated healing of both incisional wounds and full-thickness excisional
wounds in normal and ischemic skin. In all of these studies, the accelerated
healing was associated with increased neovascularization across the incision
or in the granulating wound bed. Studies in a rat fracture model have also
shown that TP508 accelerates the rate of fracture repair. Gene array analysis
of fracture callus from control and TP508-treated fractures indicated that
TP508 treatment was associated with an up-regulation of early response
elements, inflammatory mediators, and genes related to angiogenesis. Similar
to what had been seen in dermal wounds, histology from rat fracture callus
twenty-one days after treatment indicated that fractures treated with TP508
had significantly more large functional blood vessels than did fractures in
the control animals. In vitro studies support these in vivo data and indicate
that TP508 may have a direct angiogenic effect by promoting the rate of new
vessel growth.
The results from phase-1 and phase-2 human clinical studies have shown a
positive stimulatory effect of TP508 in the healing of diabetic ulcers and in
the repair of fractures to the distal aspect of the radius. Collectively,
these studies suggest that TP508 accelerates tissue repair by initiating a
cascade of events that lead to an increased rate of tissue revascularization
and regeneration.