Idiopathic pulmonary fibrosis (IPF)
Nonalcoholic steatohepatitis (NASH)
Other fibrotic diseases
Lysophosphatidic acid receptor
1 (LPA1) selective antagonist
Non-clinical studies (including the studies belonging to GLP) are ongoing.
What is idiopathic pulmonary fibrosis (IPF)?
- IPF is a type of interstitial lung disease of unknown etiology. Inflammation within the wall of alveoli lead to thickening and scarring (“fibrosis”) of the alveoli; as a result, the gas exchange efficiency of breathing decreases.
- IPF patients often notice breathlessness when engaging in activities of daily living, such as walking or bathing (“shortness of breath with exercise”).
- IPF has an extremely poor prognosis, with an average lifespan of three to five years after diagnosis. Acute exacerbation of IPF caused by other acute events such as infection is defined as a sudden acceleration of the disease that leads to a significant increase in mortality rate.
- IPF is a rare disease that affects 150,000 people in the US and 13,000 in Japan.
What is nonalcoholic steatohepatitis (NASH)?
- A condition caused by a buildup of fat in the liver affecting people who are not alcoholics is called nonalcoholic fatty liver disease (NAFLD). NAFLD is strongly associated with obesity, diabetes mellitus, hyperlipidemia, and hypertension.
- NAFLD is classified into two subtypes: nonalcoholic fatty liver (NAFL), which is benign and non-progressive, and nonalcoholic steatohepatitis (NASH), which is more severe and progressive.
- NASH is characterized by inflammation and scarring with its inherent risk of progression to hepatic cirrhosis and hepatocellular carcinoma.
- Although it is not clear how many people have NASH, it is closely associated with lifestyle-related diseases.
Mechanism of LPA1 selective antagonist
- It is thought that LPA1 is related to fibroblast migration and proliferation, collagen synthesis, and cytokine production.
- There are six known receptors of LPA (LPA 1-6). The association of LPA1 receptor with fibrotic disease has been reported as LPA1 receptor is specifically expressed in fibroblast and the expression is enhanced in patients with fibrotic diseases.
- An LPA1 selective antagonist is expected to be effective in the treatment of fibrotic diseases by selectively binding with LPA1 receptor and inhibiting its activity.