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P4–435: PBT2, a novel MPAC for the treatment of Alzheimer's disease
Author(s) -
Cherny Robert A.,
Barnham Kevin J.,
Bush Ashley I.,
Cappai Roberto,
Gautier Elisabeth C.L.,
Masters Colin L.,
Carrington Darryl,
Kocak Gulcan,
Volitakis Irene,
Kok Gaik B.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2177
Subject(s) - clioquinol , pharmacology , chemistry , in vivo , toxicity , pharmacokinetics , amyloid (mycology) , neurodegeneration , biochemistry , medicine , biology , disease , inorganic chemistry , microbiology and biotechnology , organic chemistry
infected cells. Results: Three Mabs were found capable of complete and permanent abrogation of PrP from infected N2a cells: 6D11 (PrP residues 93-109; IC50 0.47 0.06 M), 7H6 (PrP residues 130-140; IC50 1.07 0.13 M) and 7A12 (PrP residues 143-155; IC50 2.35 0.34 M). In addition, 6D11 Mab was especially effective in preventing N2a cells from de novo infection. Fluorescently labeled Mabs were found to inhibit PrP formation both on the cell surface and after internalization in the cytosol. Treatment with Mabs was not associated with toxicity in infected N2a cells nor resulted in a decreased level of PrP or other proteins. Preliminary animal studies demonstrated that administration of 6D11 Mab following prion inoculation reduced the accumulation of PrP in the lymphatic system. Conclusions: Results of our in vitro and in vivo studies indicate that anti-PrP Mabs constitute a potentially effective and safe therapeutic approach for preventing symptoms of prionoses following extracerebral exposure. Therapeutic effect of anti-PrP Mabs appears to be epitope dependent. Supported by NIH grants AG24847 and NS47433.