Discovering significant breakthroughs in fibrosis.

OUR SCIENCE

Blade is founded on a commitment to revolutionize the treatment of debilitating fibrotic diseases.

Fibrosis is a complex, pathologic process characterized by the thickening or scarring of organ tissue in response to cell/tissue damage or inflammation. Once afflicted, the tissue no longer functions normally. Fibrosis may overwhelm organs that include the liver, lung, skin, kidney, joints and eye. Fibrotic diseases are incurable, impairing the lives of millions of people worldwide.

While the underlying pathophysiology of fibrosis is complex, research continues to enhance our understanding of the disease processes. At Blade, we are experts in novel biological pathways – including autotaxin / LPA and calpain biology – that are foundational to cell and tissue damage responses leading to fibrosis.

Autotaxin / LPA and calpains each play distinct roles within the biological pathways underlying fibrosis. Ongoing dysregulation of those pathways underlies the progression and severity of fibrosis and resulting organ dysfunction.

Autotaxin in Fibrosis

Pro-fibrotic processes are also stimulated by autotaxin, a key enzyme that plays a complementary role to calpains in various fibrotic diseases. The enzymatic function of autotaxin generates extracellular lysophosphatidic acid (LPA) which acts via the LPA receptors in tissues to promote the fibrotic processes. Working through an overlapping but complementary process, the autotaxin/LPA pathway also activates myofibroblast cells that play a role in fibrosis.

Increased autotaxin levels and activity are associated with liver, lung, kidney and skin fibrosis, and levels correlate with fibrosis severity in various liver diseases (NAFLD/NASH, viral hepatitis, ALD, cirrhosis). Inhibition of the autotaxin/LPA receptor pathway has been clinically validated in idiopathic pulmonary fibrosis (IPF).

Blade Autotaxin image

References

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Matralis, 2019, Med Res Rev. 39(3):976.

Maher, 2018, Lancet Resp Med. 6(8):627.

Palmer, 2018, Chest. 154(5):1061.

Tager, 2012, Am J Respir Cell Mol Biol. 47(5):563-5.