Anti-PrP Mab 6D11 suppresses PrPSc replication in prion infected myeloid precursor line FDC-P1/22L and in the lymphoreticular system in vivo

NEUROBIOLOGY OF DISEASE

卷:34

Article

Sadowski, Martin J.^1,2,3  Pankiewicz, Joanna¹  Prelli, Frances¹  Scholtzova, Henrieta¹  Spinner, Daryl S.⁵  Kascsak, Regina B.⁵  Kascsak, Richard J.⁵  Wisniewski, Thomas^1,4,5 

[1] NYU, Sch Med, Dept Neurol, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA

[3] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA

[4] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[5] New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA

关键词: Monoclonal antibodies;    Scrapie;    Neuroinvasion;    Prion;    Treatment;    Creutzfeldt-Jakob disease;   

DOI  :  10.1016/j.nbd.2009.01.013

来源: Elsevier

【 摘 要 】

The pathogenesis of prion diseases is related to conformational transformation of cellular prion protein (PrPC) into a toxic, infectious, and self-replicating conformer termed PrPSc. Following extracerebral inoculation, the replication of PrPSc is confined for months to years to the lymporeticular system (LRS) before the secondary CNS involvement results in occurrence of neurological symptoms. Therefore, replication of PrPSc, in the early stage of infection can be targeted by therapeutic approaches, which like passive immunization have limited blood-brain-barrier penetration. in this study, we show that 6D11 anti-PrP monoclonal antibody (Mab) prevents infection on a FDC-P1 myeloid precursor cell line stably infected with 22L mouse adapted scrapie strain. Passive immunization of extracerebrally infected CD-I mice with Mab 6D11 resulted in effective suppression of PrPSc replication in the LRS. Although, a rebound of PrPSc presence occurred when the Mab 6D11 treatment was stopped, passively immunized mice showed a prolongation of the incubation period by 36.9% (p<0.0001) and a significant decrease in CNS pathology compared to control groups receiving vehicle or murine IgG. Our results indicate that antibody-based therapeutic strategies can be used, even on a short-term basis, to delay or prevent disease in subjects accidentally exposed to prions. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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