The fibroblast is a mobile, critical cell type paramount in the construction, degradation, and reconstruction of the ECM (extracellular matrix). ECM is the supporting structure and communication medium to which other cell types adhere to and interact. It can be loosely arranged, or form more rigid structures like membranes, and cartilage. It is also key to executing the proper immune response. When activated in disease, the fibroblast transitions to an an activated cell known as a myofibroblast. The myofibroblast produces both an abnormal ECM, abnormal adhesion to the ECM, and an improper immune response, all driving disease progression in fibrosis. In another form of injury, where a cancer cell is created, the activated fibroblast is termed a "cancer associated fibroblast" or CAF, and it drives tumor formation, progression and spread (metastasis).
BLR has developed therapeutic biomolecules that are based on a natural occurring set of related proteins (the CCN family) that together modulate the conversion of normal fibroblasts to myofibroblasts in normal wound healing, but fail to properly regulate with chronic injury resulting in fibrosis and/or cancer. BLR's biomolecule therapeutics target specific pro-inflammatory and pro-fibrotic elements, thus blocking progression to fibrosis, or solid tumor cancers, and a return to the normal healthy, homeostatic state.
Modern medical practice, although quite successful in treating acute disease, remains seriously lacking when it comes to treating chronic, genetic based, and orphan diseases. Abnormal wound healing is key to the development of many of these diseases, chief being various forms of fibrosis and cancer. Key to disease development is a chronic insult and the alteration of the cell’s ability to interact in a normal fashion with the surrounding microenvironment including the ECM.
Current chemotherapeutic and immunotherapeutic (I/O)- based drugs are characteristically limited in solid tumor treatment due to strong side-effects, induced chemoresistance, and/or an inability to reach all tumor cells. This results in a limited patient susceptibility and less than optimal outcome for many. BLR Bio therapeutics alone shrink tumors, but also have the potential to greatly enhance the effectiveness of chemo- and I/O therapy as combination drugs, as shown in our animal modeling studies. They may also allow for lower doses of the conventional drugs with reduced side effects. The technology is uniquely positioned with no direct competitors.
Photo at right: Human myofibroblasts identified by immunofluorescent staining of biomarkers Vinculin (left) and Smooth Muscle Actin (right). Photos credited to Drs. Shangxi Liu and Andrew Leask.