The treatment of ischemic stroke remains one of the most challenging areas of medicine today. At present, only one agent is approved (Alteplase, rt-PA). However, since symptomatic and fatal hemorrhage is more common in patients receiving t-PA than in those receiving placebo, it has been recommended that thrombolytics be used for only a brief window of time (onset of symptoms less than three hours) and only in the event that emergency back-up resources are available to handle such complications. This along with concerns within the physician community of bleeding underlie US figures showing that t-PA is administered to less than 3% of acute ischemic stroke patients. Most patients therefore receive only palliative care. LeadDiscovery has recently updated a DiscoveryDossier describing studies by scientists at ThromboGenics Ltd demonstrating that deletion of the coagulation cascade protein, alpha-2-antiplasmin, reduces stroke in a model of total cerebral artery occlusion. This dossier also reports similar results on stroke reduction following the administration of pharmacologic doses of microplasmin, a truncated form of the natural protein (plasmin) bound by alpha-2-antiplasmin. Given these promising preclinical results, ThromboGenics are entering microplasmin into Phase I investigation in man thus advancing this strategy for the acute treatment of ischemic stroke. Free access to a full overview supporting this therapeutic use of microplasmin can be gained by clicking here. US researchers working in collaboration with ThromboGenics have recently published further data supporting this concept. This group embolized rabbits by injecting small blood clots into the cerebral circulation. Microplasmin, infusion starting 60 min post-embolization, significantly reduced neurological deficits at 4 mg/kg. At this dose microplasmin was subsequently determined to be safe in a second model of stroke, since it did not increase the incidence of hemorrhages compared to vehicle-treated rabbits, nor did it significantly alter hemorrhage volume, infarct rate or volume. In contrast, t-PA, at a dose that reduced neurological deficits significantly increased hemorrhage rate compared to vehicle controls a finding that is in agreement with clinical data. This study therefore suggests that microplasmin may be as effective as t-PA in treating the effects of ischemic stroke, but with an improved safety profile. This supports the further development of microplasmin as an alternative to t-PA.

November, 2002

Adapted from Lapchak et al, Stroke 2002 Sep;33(9):2279-84

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