Lead Product

Human Recombinant Tissue Kallikrien (rhKLK-1) Protein

Tissue kallikreins all possess protease activity with a substrate specificity similar to that of trypsin or chymotrypsin. The most well-characterized activity of KLK1 is its enzymatic cleavage of kininogen to produce bradykinin (BK)-like peptides, collectively known as kinins, which activate, either directly or indirectly, subtypes of both bradykinin receptors (BK-B1, BK-B2). Activation of BK receptors by kinins set in motion a large number of complex metabolic pathways in response to ischemia within the body, which can include improved blood flow (through vasodilation), an anti-inflammatory response, cell repair through angiogenesis or vasculogenesis, and decrease of apoptosis. There is a large body of scientific studies that show tissue kallikrein-mediated release increases blood flow in a variety of tissues including kidney and heart1 and that this is likely the primary mode by which kallikrein treatment addresses brain pathologies caused by acute ischemic stroke (AIS) and kidney diseases.

MOA

DiaMedica believes DM199 has the potential to treat a broad spectrum of clinical scenarios where re-establishing blood flow and reducing inflammation in patients is vital to preserving organ function (e.g. brain, kidney, and heart).

 

 

  1. Stone, O.A., et al. Critical role of tissue kallikrein in vessel formation and maturation: implications for therapeutic revascularization. Arterioscler Thromb Vasc Biol. 2009; 29: 657–664.