FIBROTIC DISEASE

Fibrosis is a pathologic process, which includes scar formation and over production of extracellular matrix, by the connective tissue, as a response to tissue damage. Damage to tissue can result from a variety of stimuli including autoimmune reactions and mechanical injury.

 

The repair process typically involves two distinct phases: a regenerative phase, in which injured cells are replaced by cells of the same type, leaving no lasting evidence of damage; and a phase know as fibroplasia or fibrosis, in which connective tissues replaces normal parenchymal tissue.  Although initially beneficial, the repair process becomes pathogenic when it is not controlled appropriately, resulting in substantial deposition of extracellular matrix component in which normal tissue is replaced with permanent scar tissue. Pathologies include: in the skin pathologic scarring such as keloids and hypertrophic scarring, cirrhosis of liver and gallbladder, in the heart and the kidneys, pulmonary and bone-marrow fibrosis, and scleroderma.

 

The process of tissue repair is complex, and it has been known for some time that healing can be regenerative or scar forming. It is now appreciated that permanent scarring takes a very long time to develop and the process is dynamic. Many patients suffer from fibrotic diseases and the overall aim is to develop anti-fibrotic agents, targeted to the pathologic molecular process. Thus, targeting a key participant  in this process such as extracellular GzmB to achieve a state favoring regenerative repair should provide opportunity to not only beneficially influence outcome in repair, but also to affect reversal of fibrosis.

 

INDICATIONS

 

Idiopathic Pulmonary Fibrosis

Cardiac Fibrosis