Probiodrug AG Release: Amyloid-beta (Abeta) Aggregate-Clearing By The Murine Anti-Pyroglutamate-3 Abeta IgG2a Monoclonal Antibody PBD-C06 With And Without A Complement Mutation In An Alzheimer’s Mouse Model
11/16/2016 10:01:46 AM
HALLE (SAALE), Germany, 16 November 2016 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), announced today the first results of a preclinical study in an AD mouse model with the pyroglutamate-3 Abeta (pGlu3-Abeta)-specific antibody mPBD-C06, comparing versions with and without a mutation eliminating complement activation which will be presented as a poster at the Society for Neuroscience (SfN) meeting on 16 November 2016 in San Diego, CA.
Data were generated in collaboration with Cynthia Lemere of Brigham and Women’s Hospital, Harvard Medical School, and QPS, Graz, Austria.
Previously, Lemere’s team showed that the mouse IgG2a variant of the anti-pGlu3-Abeta monoclonal antibody was more effective at clearing Abeta aggregates and rescued behavioral deficits compared to the mouse IgG1 version (SfN 2015). In the present study, the effect of eliminating the antibody’s ability to activate complement (CDC) on the efficiency to reduce Abeta plaques was investigated and it was found that both variants - with and without CDC - reduced pGlu3-Abeta as well as general Abeta to the same extent - without inducing microhemorrhages. Thus, avoiding complement activation did not impact the capacity of mPBD-C06 to eliminate pGlu3-Abeta aggregates. In addition, microglial activation was assessed in vivo by 18F-GE180 TSPO microPET imaging at baseline and following a single injection of the pGlu3-Abeta antibody variants. In contrast to the IgG2a variant, which showed enhanced whole brain uptake of 18F-GE180 in AD mice, the antibody lacking CDC did not alter the TSPO signal after injection.
In summary, the data demonstrate for the first time, that microglial activation, analyzed by TSPO microPET, can be reduced by CDC inactivation without impairing the potency of the antibody to clear amyloid deposits. Further studies are underway to better understand the clearance mechanisms for each of these anti-pGlu3 Abeta antibodies.
Inge Lues, Chief Development Officer of Probiodrug, commented: “These data are very exciting as they demonstrate efficient Abeta clearance without potential side- or dose-limiting effects of inducing inflammation.”
Cynthia Lemere, PhD, scientist at Brigham and Women’s Hospital, added: “Although further investigation is needed, these early data suggest that the novel CDC-mutant anti-pGlu3 Abeta antibody may improve efficacy and safety as an AD immunotherapy.” Lemere is currently the recipient of pre-clinical sponsored research from Probiodrug AG.
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