Science

 

 

 

Catena focuses its research and product development efforts around manipulation of the biology of the blood-borne signaling molecule lysophosphatidic acid (LPA).  Catena’s products will either block the signaling of LPA, reduce production of LPA, or mimic LPA.

 

Molecular Structure of Lysophosphatidic Acid

 

 

 

Lysophosphatidic Acid

Lysophosphatidic acid (LPA) is a simple lipid (fat molecule) with many important biological functions.  LPA has a long carbon-chain structure characteristic of all lipid molecules.  This long carbon chain was the inspiration for the name of the company; “catena” is the Latin word for “chain.”  LPA regulates cellular proliferation, cellular migration, cellular differentiation, angiogenesis, tumor cell invasion, and wound healing.  LPA exists in serum, and is among the same family of molecules as sphingosine-1-phosphate (S1P), a recognized bioactive lipid mediator involved in lymphocyte trafficking; drugs targeting the effects of S1P are in late stage clinical development (e.g., FTY720 by Novartis) and in early development at most pharmaceutical companies. 

 

LPA and Ovarian Cancer

LPA is involved in the pathophysiology of cancer, particularly so in ovarian cancer.  Ovarian cancer remains a difficult to diagnose and poorly treated tumor type, resulting in poor 5-year survival rates of around one third of patients.  90% of ovarian cancer patients have LPA levels increased in their blood.  Those afflicted with ovarian cancer experience a build up of fluid in their peritoneal cavity called ascites, causing their abdomen to become distended.  This fluid contains 100-times as much LPA as would be expected during normal health, and this LPA acts as a potent cancer growth factor.  Ovarian cancer cells also over-express LPA receptors.  Genetic ‘knock-down’ of LPA receptors using RNA-interference reduces ovarian cancer cell migration and invasion.  Not surprisingly, LPA receptors are considered an attractive target for cancer therapy, particularly ovarian cancer.

 

LPA and Organ Fibrosis

LPA is also suspected as an agent involved in organ fibrosis.  Fibrosis refers to the formation or deposition of excessive amount of fibrous connective tissue in an organ, resulting in a detrimental stiffening or hardening of the organ, eventually leading to reduced function or even failure of the organ.  There are three organs where fibrosis is a significant problem: the lungs, the liver, and the kidneys.  A 2008 study demonstrated that mice which lack an LPA receptor 1 are protected from development of pulmonary fibrosis.  Furthermore, in the same study, all mice without LPA receptor 1 survived fibrosis, whereas other fibrotic mice had a mortality rate of 50%.  Finally, cells taken from the lungs of IPF patients had higher expression of LPA receptor 1, and associated lung fluid had higher levels of LPA.  Similar results have been generated in renal (kidney) fibrosis models. Taken together, anti-LPA therapy is a promising approach to treatment of organ fibrosis.