Fibrotic conditions usually occur as a result of a disturbed woundhealing process after trauma or chronic inflammation. The fibrotic pathology is especially prevalent in organs that are on a regular basis exposed to chemical and biological insults, e.g. liver, lung, skin and kidney. Regardless if the disorder is acute or chronic they share a common characteristic of abnormal fibroblast activation and accumulation of extracellular matrix (ECM), leading to a loss of organ function as the normal tissue is replaced by scar tissue. The condition is progressive, often irreversible with a poor prognosis and survival rate.
The composition of fibrotic scarring is quite similar irrespective of the cause of injury. Diagnosis and the verification of the severity of fibrosis are of utmost importance from prognostic viewpoints. The decision-making process for treatment is highly based on the assessment of fibrosis, its progression and the onset of complications. In hepatic fibrosis, percutaneous liver biopsy is the gold standard for grading and staging of liver disease. This is, however, an invasive procedure with certain unavoidable risks and complications commonly associated with pain and discomfort. Death rates, due to complications from the procedure, range from 1:1000 to 1:10 000 (Crockett et al., 2006).
Levels of serum monoamine oxidase activity have been found to be elevated in patients with cirrhosis, chronic hepatitis and liver cancer associated with fibrosis but were found to be normal in patients with inflammatory connective tissue disorders such as rheumatoid arthritis or systemic lupus erythematosus (McEwen and Castell 1967, J Lab Clin Med. 70:36-47; Ito et al. 1971 Digestion. 4:49-58; Ma Lin et al., 1976, Proc Soc Exp Biol Med. 151:40-3). However, the elevated serum monoamine oxidase activity has been considered only as a marker or as a response to tissue injury and has not been known to have a role in the pathogenesis of fibrosis.
Conventional therapeutic approaches have largely been targeted towards the inflammatory process of fibrosis, using corticosteroids and immunosuppressive drugs. However, unfortunately these agents have little to no clinical effect and there is a clear need for new drugs to treat fibrotic conditions.
USPTO Backgrounds
USPTO Backgrounds