Download PDF
Thromb Haemost 2009; 102(03): 606-608
DOI: 10.1160/TH09-02-0114
Letters to the Editor
Schattauer GmbH

PPACK-Desmodus rotundus salivary plasminogen activator (cDSPAα1) prevents the passage of tissuetype plasminogen activator (rt-PA) across the blood-brain barrier and neurotoxicity

Benoit D. Roussel   *
1   INSERM, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, CNRS, UMR CNRS 6232 CINAPs “Center for Imaging Neurosciences and Applications to Pathologies”, Cyceron, Caen Cedex, F-14074 France; University of Caen Basse-Normandie, Caen Cedex, France
,
Yannick Hommet   *
1   INSERM, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, CNRS, UMR CNRS 6232 CINAPs “Center for Imaging Neurosciences and Applications to Pathologies”, Cyceron, Caen Cedex, F-14074 France; University of Caen Basse-Normandie, Caen Cedex, France
,
Richard Macrez
1   INSERM, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, CNRS, UMR CNRS 6232 CINAPs “Center for Imaging Neurosciences and Applications to Pathologies”, Cyceron, Caen Cedex, F-14074 France; University of Caen Basse-Normandie, Caen Cedex, France
,
Torsten Schulz
2   PAION Deutschland GmbH, Aachen, Germany
,
Karl-Uwe Petersen
2   PAION Deutschland GmbH, Aachen, Germany
,
Vincent Berezowski
3   Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, EA 2465, IFR114-IMPRT, Université d’Artois, Faculté des Sciences Jean Perrin, France
,
Roméo Cecchelli
3   Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, EA 2465, IFR114-IMPRT, Université d’Artois, Faculté des Sciences Jean Perrin, France
,
Carine Ali
1   INSERM, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, CNRS, UMR CNRS 6232 CINAPs “Center for Imaging Neurosciences and Applications to Pathologies”, Cyceron, Caen Cedex, F-14074 France; University of Caen Basse-Normandie, Caen Cedex, France
,
Denis Vivien
1   INSERM, INSERM U919, Serine Proteases and Pathophysiology of the neurovascular Unit, CNRS, UMR CNRS 6232 CINAPs “Center for Imaging Neurosciences and Applications to Pathologies”, Cyceron, Caen Cedex, F-14074 France; University of Caen Basse-Normandie, Caen Cedex, France
› Author AffiliationsFinancial support: This study was supported in part by research funding from PAION Deutschland GmbH.
Further Information

Publication History

Received: 23 February 2009

Accepted after major revision: 23 June 2009

Publication Date:
22 November 2017 (online)

Also available at
    Permissions and Reprints

 

* These authors contributed equally to this work.


 

  • References

  • 1 NINDS. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study GroupTissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333: 1581-1587.
    PubMedGoogle Scholar
  • 2 Tsirka SE, Gualandris A, Amaral DG. et al. Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 1995; 377: 340-344.
    CrossrefPubMedGoogle Scholar
  • 3 Nicole O, Docagne F, Ali C. et al. The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat Med 2001; 07: 59-64.
    CrossrefPubMedGoogle Scholar
  • 4 Schleuning WD, Alagon A, Boidol W. et al. Plasminogen activators from the saliva of Desmodus rotundus (common vampire bat): unique fibrin specificity. Ann NY Acad Sci 1992; 04: 395-403.
    PubMedGoogle Scholar
  • 5 Reddrop C, Moldrich RX, Beart PM. et al. Vampire bat salivary plasminogen activator (desmoteplase) in-hibits tissue-type plasminogen activator-induced potentiation of excitotoxic injury. Stroke 2005; 36: 1241-1246.
    CrossrefPubMedGoogle Scholar
  • 6 López-Atalaya JP, Roussel BD, Ali C. et al. Recombinant Desmodus rotundus salivary plasminogen activator crosses the blood-brain barrier through a lowdensity lipoprotein receptor-related protein-dependent mechanism without exerting neurotoxic effects. Stroke 2007; 38: 1036-1043.
    CrossrefPubMedGoogle Scholar
  • 7 Cecchelli R, Dehouck B, Descamps L. et al. In vitro model for evaluating drug transport across the bloodbrain barrier. Adv Drug Deliv Rev 1999; 136: 165-178.
    PubMedGoogle Scholar
  • 8 Benchenane K, Berezowski V, Ali C. et al. Tissuetype plasminogen activator crosses the intact bloodbrain barrier by low-density lipoprotein receptor-related protein-mediated transcytosis. Circulation 2005; 111: 2241-2249.
    CrossrefPubMedGoogle Scholar
  • 9 Hacke W, Albers G, Al-Rawi Y. et al. DIAS Study Group. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke 2005; 36: 66-73.
    CrossrefPubMedGoogle Scholar
  • 10 Hacke W, Furlan AJ, Al-Rawi Y. et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 2009; 08: 141-150.
    CrossrefPubMedGoogle Scholar
  • 11 Warach S. for the DIAS-2 Study Group. Clinical benefit of desmoteplase treatment in patients with moderate to severe stroke—further results of the DIAS-2 Study. Abstract presented at the International Stroke Conference; New Orleans; February. 21. 2008
    PubMedGoogle Scholar