Preclinical toxicological assessment of a novel monoclonal antibody targeting human platelet-derived growth factor CC (PDGF-CC) in PDGF-CChum mice

PloS One
Manuel ZeitelhoferUlf Eriksson

Abstract

Platelet-derived growth factor CC (PDGF-CC) is important during foetal development but also in pathogenesis of neurologic diseases, cancer and fibrosis. We have previously demonstrated that blocking the PDGF-CC/PDGF receptor alpha (PDGFRα) axis resulted in reduction of stroke volume and cerebrovascular permeability after experimentally induced stroke. Recently, we could translate these findings into the clinic showing that imatinib, a small tyrosine kinase inhibitor targeting PDGF receptors, can significantly improve neurological outcome after ischemic stroke in human. Herein we report preclinical toxicological analyses of our newly generated monoclonal anti-human PDGF-CC antibody 6B3 (mAb 6B3) in PDGF-CC humanized mice. Beside histological organ assessment, we also analysed serum, urine, haematological parameters and the general health status of the treated mice. We could not find any indications that mAb 6B3 is toxic or has other significant side effects neither in short, nor in long treatment regimens. Our results indicate that mAb 6B3 can be further developed for clinical use. This opens up the possibility to assess the therapeutic potential of blocking PDGF-CC in diverse pathological conditions such as neurologic diseases,...Continue Reading

References

May 12, 2000·Nature Cell Biology·X LiU Eriksson
Dec 18, 2001·Mechanisms of Development·Karin AaseUlf Eriksson
Jun 23, 2004·Cytokine & Growth Factor Reviews·Linda FredrikssonUlf Eriksson
Sep 17, 2004·The EMBO Journal·Linda FredrikssonUlf Eriksson
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jean S CampbellNelson Fausto
Aug 15, 2006·Advanced Drug Delivery Reviews·Leonard G Presta
Jul 6, 2007·Expert Review of Neurotherapeutics·Sonja Külkens, Werner Hacke
Jan 11, 2008·Journal of the American Society of Nephrology : JASN·Frank EitnerTammo Ostendorf
Mar 7, 2008·Blood·Seonaid M PyeJane F Apperley
Jul 2, 2009·International Journal of Cancer. Journal International Du Cancer·Yukio YamanoHideki Tanzawa
Mar 23, 2010·Nature Reviews. Drug Discovery·Trevor T HanselAndrew J T George
Jun 23, 2012·PloS One·Mathew B AbramsUlf Eriksson
Jan 3, 2013·Annals of Neurology·Richard Daneman
Aug 15, 2015·Annals of Clinical and Translational Neurology·Linda FredrikssonDaniel A Lawrence
Oct 27, 2015·Frontiers in Cellular Neuroscience·Enming J SuDaniel A Lawrence
Dec 10, 2015·Frontiers in Cellular Neuroscience·Christina StefanitschLinda Fredriksson
Dec 22, 2015·Acta Neuropathologica·Sebastian A LewandowskiUlf Eriksson
Jun 13, 2016·Lancet Neurology·William N WhiteleyUNKNOWN Stroke Thrombolysis Trialists' Collaboration
Jun 19, 2018·One Health·Paul R TorgersonNiko Speybroeck

❮ Previous
Next ❯

Citations

Jul 31, 2019·Computational and Structural Biotechnology Journal·Jan MicanJiri Damborsky

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.