Desmoteplase as a potential treatment for cerebral ischaemia.
BACKGROUND
Desmoteplase is an investigational plasminogen activator found in the saliva of the vampire bat, Desmodus rotundus. It has been of scientific interest for over 25 years as it exhibits pharmacological properties that have led to the hypothesis that desmoteplase may be safer and more effective than recombinant tissue plasminogen activator (rtPA) in arterial thromboembolic disease, and in particular, acute ischaemic stroke (AIS).


METHODS
In this review, the authors cover the pharmacological properties of desmoteplase, focussing on how this translates into a theoretical advantage over rtPA in AIS. The authors further present preclinical studies and clinical data on the use of desmoteplase in AIS.


CONCLUSIONS
In contrast to rtPA, and despite a similar structure, desmoteplase has demonstrated high selectivity for fibrin and an absence of neurotoxicity in experimental models. Demonstrating such properties in animal models, one would have expected an ambitious clinical study future. Phase II and Phase III clinical studies in patients with AIS demonstrated an excellent safety profile with low risk of symptomatic intracranial haemorrhage compared to rtPA. However, data on clinical and radiological efficacy end points of desmoteplase in AIS are inconclusive. Further Phase III trials are currently underway and their results are eagerly awaited.
Sandwell and West Birmingham Hospitals NHS Trust, City Hospital, Cardiology Department , Birmingham , UK.
Rikesh
R
Patel
Sevasti
S
Ispoglou
Stavros
S
Apostolakis
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010960:Plasminogen Activators / Q000494:pharmacology* / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy
D005343:Fibrinolytic Agents; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D010960:Plasminogen Activators
acute ischaemic stroke; desmoteplase; fibrin selectivity; neurotoxicity; plasminogen activator; thrombolysis