Desmoteplase

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Desmoteplase
Desmoteplase
Structure according to 1A5I
Enzyme classification
EC, category 3.4.21.68 ,  peptidase

Desmoteplase is an experimental drug , the for the treatment of ischemic to be inserted stroke. It is also called Desmodus rotundus Plasminogen Activator Salivary designated (DSPA), or Draculin and is a 411 of amino acids existing enzyme .

Natural occurrence

The Common Vampire ( Desmodus rotundus )

Desmoteplase is found in the saliva of some vampire bats , such as the common vampire ( Desmodus rotundus ) and was first described in 1966. As a natural plasminogen activator , it prevents blood that the bat drinks from clotting . After a vampire bite, blood can flow out of the wound for up to eight hours.

As a drug

Because of its anticoagulant properties, Desmoteplase is a potential drug for the treatment of heart attacks and strokes. A recombinant form of the enzyme is in clinical trials in stroke. The recombinant protein was developed between 1988 and 1991 under the name DSPA (Desmodus rotundus Salivary gland Plasminogen Activator) in the laboratories of Schering AG Berlin, and after Schering's cardiovascular research was discontinued, it was sold to the Paion company. Desmoteplase is currently not approved as a drug and has been developed for approval by the Lundbeck company since 2012, after all rights remaining with Paion were taken over . It is currently in phase III clinical trials.

The safety of use in humans was investigated in two phase II studies. There were also indications that Desmoteplase could have a beneficial effect on the clinical course after a stroke.

However, in contrast to the previous studies, another clinical study by the manufacturer showed that Desmoteplase does not offer a significant advantage compared to placebo . After further evaluations, however, PAION and Lundbeck declared that they wanted to continue the development.

literature

  • J. Kraetzschmar, B. Haendler, G. Langer, W. Boidol, P. Bringmann, A. Alagon, P. Donner, WD Schleuning: The plasminogen activator family from the salivary gland of the vampire bat: cloning and expression. In: Genes. Volume 105, 1991, pp. 229-237.
  • R. Apitz-Castro, S. Béguin, A. Tablante, F. Bartoli, JC Holt, HC Hemker: Purification and partial characterization of draculin, the anticoagulant factor present in the saliva of vampire bats (Desmodus rotundus). In: Thrombosis and Haemostasis . Volume 73, Number 1, January 1995, pp. 94-100. PMID 7740503 .
  • AZ Fernandez, A. Tablante, F. Bartoli, S. Beguin, HC Hemker, R. Apitz-Castro: Expression of biological activity of draculin, the anticoagulant factor from vampire bat saliva, is strictly dependent on the appropriate glycosylation of the native molecule . In: Biochimica et Biophysica Acta . Volume 1425, Number 2, October 1998, pp. 291-299. PMID 9795244 .
  • AZ Fernandez, A. Tablante, S. Beguín, HC Hemker, R. Apitz-Castro: Draculin, the anticoagulant factor in vampire bat saliva, is a tight-binding, noncompetitive inhibitor of activated factor X. In: Biochimica et Biophysica Acta . Volume 1434, Number 1, September 1999, pp. 135-142. PMID 10556567 .

Individual evidence

  1. ^ C. Hawkey: Plasminogen activator in saliva of the vampire bat Desmodus rotundus. In: Nature. 211, 1966, pp. 434-435. PMID 5967844 .
  2. ↑ D. Ma, DM Mizurini et al: Desmolaris, a novel factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in vivo. In: Blood. Volume 122, number 25, December 2013, pp. 4094-4106, doi: 10.1182 / blood-2013-08-517474 . PMID 24159172 . PMC 3862280 (free full text).
  3. ↑ T. Steiner, E. Jüttler, P. Ringleb: Acute Therapy of Stroke. In: Neurologist. 78, 2007, pp. 1147-1154. PMID 1787907 .
  4. ^ W. Hacke, G. Albers, Y. Al-Rawi et al.: The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. In: Stroke. 36, 2005, pp. 66-73. PMID 15569863 .
  5. ↑ AJ Furlan, D. Eyding, GW Albers et al: Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. In: Stroke. 37, 2006, pp. 1227-1231. PMID 16574922 .
  6. ↑ PAION AG: Press release from May 31, 2007 ( Memento of the original from May 19, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 24 kB), accessed on August 21, 2009. @1@ 2Template: Webachiv / IABot / www.paion.de
  7. ↑ PAION AG: Press release from October 18, 2007. ( Memento of the original from May 19, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. (PDF; 24 kB), accessed on August 21, 2009. @1@ 2Template: Webachiv / IABot / www.paion.de

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