Safety evaluation of a recombinant plasmin derivative lacking kringles 2-5 and rt-PA in a rat model of transient ischemic stroke

Experimental and Translational Stroke Medicine

Volumn 4, Issue 1, 2012, Pages

  Crumrine, R C ^a   Marder, Victor J ^b   Taylor, G M ^a   LaManna, Joseph C ^c   Tsipis, Constantinos P ^c   Novokhatny, Valery ^a   Scuderi, Philip ^a   Petteway, Stephen R ^a   Arora, Vikram ^a  

^a Grifols Therapeutics Inc   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Intracranial hemorrhage; Ischemic stroke; Middle cerebral artery occlusion (MCAo); Recombinant tissue type plasminogen activator (rt PA); Spontaneously hypertensive rat model; (K2 K5) plasmin

Indexed keywords

DELTA K2 K5 PLASMIN; FIBRINOLYTIC AGENT; RECOMBINANT PLASMINOGEN ACTIVATOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD CLOT LYSIS; BRAIN HEMORRHAGE; BRAIN INFARCTION SIZE; CLINICAL EVALUATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; KRINGLE DOMAIN; LOW DRUG DOSE; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NONHUMAN; PRIORITY JOURNAL; RAT; SPONTANEOUSLY HYPERTENSIVE RAT; TEMPORAL LOBE; TRANSIENT ISCHEMIC ATTACK;

EID: 84866411637     PISSN: None     EISSN: 20407378     Source Type: Journal    
DOI: 10.1186/2040-7378-4-10     Document Type: Article

References (48)

1. . NINDS (rt-PA Stroke Study Group): Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995, 333:1581-1587.
2. Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008, 359:1317-1329. 10.1056/NEJMoa0804656, 18815396.
3. Hunt JA, Petteway SR, Scuderi P, Novokhatny V. Simplified recombinant plasmin: production and functional comparison of a novel thrombolytic molecule with plasma-derived plasmin. Thromb Haemost 2008, 100:413-419.
4. Marder VJ, Manyak S, Gruber T, Goyal A, Moreno G, Hunt J, Bromirski J, Scuderi P, Petteway SR, Novokhatny V. Haemostatic safety of a unique recombinant plasmin molecule lacking kringles 2-5. Thromb Haemost 2010, 104:780-787. 10.1160/TH09-10-0742, 20806125.
5. Marder VJ. Historical perspective and future direction of thrombolysis research: the re-discovery of plasmin. J Thromb Haemost 2011, 9(Suppl 1):364-373.
6. Marder VJ, Landskroner K, Novokhatny V, Zimmerman TP, Kong M, Kanouse JJ, Jesmok G. Plasmin induces local thrombolysis without causing hemorrhage: a comparison with tissue plasminogen activator in the rabbit. Thromb Haemost 2001, 86:739-745.
7. Marder VJ, Novokhatny V. Direct fibrinolytic agents: biochemical attributes, preclinical foundation and clinical potential. J Thromb Haemost 2010, 8:433-444. 10.1111/j.1538-7836.2009.03701.x, 19943877.
8. Stewart D, Kong M, Novokhatny V, Jesmok G, Marder VJ. Distinct dose-dependent effects of plasmin and TPA on coagulation and hemorrhage. Blood 2003, 101:3002-3007. 10.1182/blood-2002-08-2546, 12446443.
9. Marder VJ, Jahan R, Gruber T, Goyal A, Arora V. Thrombolysis with plasmin: implications for stroke treatment. Stroke 2010, 41:S45-49. 10.1161/STROKEAHA.110.595157, 3212867, 20876504.
10. Crumrine RC, Marder VJ, Taylor GM, LaManna JC, Tsipis CP, Novokhatny V, Scuderi P, Petteway SR, Arora V. (k2-k5)Plasmin (TAL6003) is an effective and safe direct acting thrombolytic as compared to rtPA: implications for stroke therapy. In CIRSE 2011; Munich, Germany. 2011 (Abstract) , : . 3298647, 22011783.
11. Crumrine RC, Marder VJ, Taylor GM, Lamanna JC, Tsipis CP, Scuderi P, Petteway SR, Arora V. Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model. Exp Transl Stroke Med 2011, 3:10. 10.1186/2040-7378-3-10, 3184064, 21933438.
12. Lisboa RC, Jovanovic BD, Alberts MJ. Analysis of the safety and efficacy of intra-arterial thrombolytic therapy in ischemic stroke. Stroke 2002, 33:2866-2871. 10.1161/01.STR.0000038987.62325.14, 12468783.
13. Molina CA. Reperfusion therapies for acute ischemic stroke: current pharmacological and mechanical approaches. Stroke 2011, 42:S16-19. 10.1161/STROKEAHA.110.598763, 21164113.
14. IST-3 Study Protocol Third international stroke trial: thrombolysis for acute ischaemic stroke. [http://www.ist3.com], IST-3 Study Protocol.
15. Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Baethmann A, Reulen HJ. A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. Stroke 1998, 29:2162-2170. 10.1161/01.STR.29.10.2162, 9756599.
16. Zhao Q, Memezawa H, Smith ML, Siesjo BK. Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament. Brain Res 1994, 649:253-259. 10.1016/0006-8993(94)91071-5, 7953639.
17. Selman WR, Crumrine RC, Ricci AJ, LaManna JC, Ratcheson RA, Lust WD. Impairment of metabolic recovery with increasing periods of middle cerebral artery occlusion in rats. Stroke 1990, 21:467-471. 10.1161/01.STR.21.3.467, 2309272.
18. Selman WR, Crumrine RC, Rosenstein CC, Jenkins C, LaManna JC, Ratcheson RA, Lust WD. Rapid metabolic failure in spontaneously hypertensive rats after middle cerebral artery ligation. Metabolic brain disease 1991, 6:57-64. 10.1007/BF00999903, 1749364.
19. Selman WR, Ricci AJ, Crumrine RC, LaManna JC, Ratcheson RA, Lust WD. The evolution of focal ischemic damage: a metabolic analysis. Metabolic brain disease 1990, 5:33-44. 10.1007/BF00996976, 2336048.
20. Selman WR, Lust WD. Pathophysiology of irreversible brain damage in a rat model of focal ischemia. Neurosurgeons 1991, 10:18-27.
21. Crumrine RC, Selman WR, LaManna JC, Lust WD. Protein kinase C activity in permanent focal cerebral ischemia. Molecular and chemical neuropathology/sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid 1992, 16:85-93.
22. Finelli DA, Hopkins AL, Selman WR, Crumrine RC, Bhatti SU, Lust WD. Evaluation of experimental early acute cerebral ischemia before the development of edema: use of dynamic, contrast-enhanced and diffusion-weighted MR scanning. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine/Society of Magnetic Resonance in Medicine 1992, 27:189-197.
23. Brint S, Jacewicz M, Kiessling M, Tanabe J, Pulsinelli W. Focal brain ischemia in the rat: methods for reproducible neocortical infarction using tandem occlusion of the distal middle cerebral and ipsilateral common carotid arteries. J Cereb Blood Flow Metab 1988, 8:474-485. 10.1038/jcbfm.1988.88, 3392112.
24. Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo EH. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 2009, 40:2244-2250. 10.1161/STROKEAHA.108.541128, 2888275, 19246690.
25. Howells DW, Porritt MJ, Rewell SS, O'Collins V, Sena ES, van der Worp HB, Traystman RJ, Macleod MR. Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia. J Cereb Blood Flow Metab 2010, 30:1412-1431. 10.1038/jcbfm.2010.66, 2949237,2949237, 20485296.
26. Welsh FA, Sakamoto T, McKee AE, Sims RE. Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. J Neurochem 1987, 49:846-851. 10.1111/j.1471-4159.1987.tb00971.x, 3612129.
27. Seta KA RCC, TS W, WD L, McCandless D. Experimental models of human stroke. In Neuromethods. Volume 22. Edited by Boulton AA BG, Butterworth RF. Totowa, New Jersey: The Humana Press, Inc.; 1992: 1-50: Animal Models of Neurological Disease, II: Metabolic Encephalopathies and the Epilepsies] 1992, 22:1-50.
28. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986, 17:472-476. 10.1161/01.STR.17.3.472, 3715945.
29. Shaw GJ, Sperling M, Meunier JM. Long-term stability of recombinant tissue plasminogen activator at -80 C. BMC Res Notes 2009, 2:117. 10.1186/1756-0500-2-117, 2711093, 19566947.
30. Korninger C, Collen D. Studies on the specific fibrinolytic effect of human extrinsic (tissue-type) plasminogen activator in human blood and in various animal species in vitro. Thromb Haemost 1981, 46:561-565.
31. Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 1986, 17:1304-1308. 10.1161/01.STR.17.6.1304, 2433817.
32. Landskroner K, Olson N, Jesmok G. Cross-species pharmacologic evaluation of plasmin as a direct-acting thrombolytic agent: ex vivo evaluation for large animal model development. Journal of vascular and interventional radiology : JVIR 2005, 16:369-377. 10.1097/01.RVI.0000148828.40438.D3, 15758133.
33. Haelewyn B, Risso JJ, Abraini JH. Human recombinant tissue-plasminogen activator (alteplase): why not use the 'human' dose for stroke studies in rats?. J Cereb Blood Flow Metab 2010, 30:900-903. 10.1038/jcbfm.2010.33, 2949192, 20216551.
34. Wang CX, Ding X, Shuaib A. Treatment with melagatran alone or in combination with thrombolytic therapy reduced ischemic brain injury. Exp Neurol 2008, 213:171-175. 10.1016/j.expneurol.2008.05.020, 18598697.
35. Christou I, Alexandrov AV, Burgin WS, Wojner AW, Felberg RA, Malkoff M, Grotta JC. Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke. Stroke 2000, 31:1812-1816. 10.1161/01.STR.31.8.1812, 10926939.
36. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC. et al: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004, 363:768-774.
37. del Zoppo GJ, von Kummer R, Hamann GF. Ischaemic damage of brain microvessels: inherent risks for thrombolytic treatment in stroke. J Neurol Neurosurg Psychiatry 1998, 65:1-9. 10.1136/jnnp.65.1.1, 2170158, 9667553.
38. Gautier S, Petrault O, Gele P, Laprais M, Bastide M, Bauters A, Deplanque D, Jude B, Caron J, Bordet R. Involvement of thrombolysis in recombinant tissue plasminogen activator-induced cerebral hemorrhages and effect on infarct volume and postischemic endothelial function. Stroke 2003, 34:2975-2979. 10.1161/01.STR.0000101914.62066.7B, 14615621.
39. Kahles T, Foerch C, Sitzer M, Schroeter M, Steinmetz H, Rami A, Neumann-Haefelin T. Tissue plasminogen activator mediated blood-brain barrier damage in transient focal cerebral ischemia in rats: relevance of interactions between thrombotic material and thrombolytic agent. Vascul Pharmacol 2005, 43:254-259. 10.1016/j.vph.2005.07.008, 16185938.
40. Lewandowski CA, Frankel M, Tomsick TA, Broderick J, Frey J, Clark W, Starkman S, Grotta J, Spilker J, Khoury J, Brott T. Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke 1999, 30:2598-2605. 10.1161/01.STR.30.12.2598, 10582984.
41. Jiang Q, Zhang ZG, Zhang L, Ding GL, Li L, Ewing JR, Lu M, Whitton P, Hu J, Li QJ, et al. MRI evaluation of treatment of embolic stroke in rat with intra-arterial and intravenous rt-PA. J Neurol Sci 2004, 224:57-67. 10.1016/j.jns.2004.06.004, 15450772.
42. Shaltoni HM, Albright KC, Gonzales NR, Weir RU, Khaja AM, Sugg RM, Campbell MS, Cacayorin ED, Grotta JC, Noser EA. Is intra-arterial thrombolysis safe after full-dose intravenous recombinant tissue plasminogen activator for acute ischemic stroke?. Stroke 2007, 38:80-84. 10.1161/STROKEAHA.107.486126, 17122433.
43. Messe SR, Tanne D, Demchuk AM, Cucchiara BL, Levine SR, Kasner SE. Dosing errors may impact the risk of rt-PA for stroke: the Multicenter rt-PA Acute Stroke Survey. J Stroke Cerebrovasc Dis 2004, 13:35-40. 10.1016/j.jstrokecerebrovasdis.2004.01.001, 17903947.
44. Aronowski J, Strong R, Grotta JC. Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 1997, 17:1048-1056.
45. Overgaard K, Sereghy T, Pedersen H, Boysen G. Effect of delayed thrombolysis with rt-PA in a rat embolic stroke model. J Cereb Blood Flow Metab 1994, 14:472-477. 10.1038/jcbfm.1994.58, 8163589.
46. Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O'Brien B, Bladin C, McElduff P, Allen C, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012, 366:1099-1107. 10.1056/NEJMoa1109842, 22435369.
47. Nagai N, De Mol M, Van Hoef B, Verstreken M, Collen D. Depletion of circulating alpha(2)-antiplasmin by intravenous plasmin or immunoneutralization reduces focal cerebral ischemic injury in the absence of arterial recanalization. Blood 2001, 97:3086-3092. 10.1182/blood.V97.10.3086, 11342434.
48. Lapchak PA, Araujo DM, Pakola S, Song D, Wei J, Zivin JA. Microplasmin: a novel thrombolytic that improves behavioral outcome after embolic strokes in rabbits. Stroke 2002, 33:2279-2284. 10.1161/01.STR.0000028267.09604.7B, 12215599.