Десмотеплаза: Қан ұюды ерітетін препараттың тарихы мен тоқтатылуы

Medication

Desmoteplase is a novel, highly fibrin specific "clot busting" (thrombolytic) drug in development that reached phase III clinical trials. The Danish pharmaceutical company, Lundbeck, owns the worldwide rights to Desmoteplase. In 2009, two large trials (DIAS 3 and DIAS 4) were started to test it as a safe and effective treatment for patients with acute ischaemic stroke. After disappointing results in DIAS 3, DIAS 4 was terminated, and in December 2014 Lundbeck announced that they would stop the development of desmoteplase. Desmoteplase is a recombinant form of the alpha 1 isoform of DSPA (Desmodus rotundus salivary plasminogen activator).

Desmoteplase, a chemical found in the saliva of vampire bats, has the effect of catalysing the conversion of plasminogen to plasmin, which is the enzyme responsible for breaking down fibrin blood clots.

As early as in 1932, the saliva of the vampire bat (Desmodus rotundus) was known to lead to interference with the haemostatic mechanism of the host animal. In 1991, the DNA coding of four plasminogen activators present in the saliva of the vampire bat was completed. Of the four, recombinant D. rotundus salivary plasminogen activator alpha 1 (rDSPAα1; desmoteplase) was investigated further.

The structure of desmoteplase is similar to rt PA (alteplase), but it does not contain the plasmin sensitive cleavage site and the lysine binding Kringle 2 domain. As a result, desmoteplase, in comparison to rt PA, has high fibrin selectivity (100,000 v. 550 fold increase in catalytic activity), an absence of neurotoxicity, and no apparent negative effect on the blood–brain barrier. Desmoteplase also has a half life of about four hours; rtPA has a terminal plasma half life of about 5 minutes.