euro-toxicology-2016_scientifictracks-abstracts

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Volume 6, Issue 6(Suppl) J Clin Toxicol 2016
ISSN: 2161-0495, JCT an open access journal
Page 48
Notes:
Euro Toxicology 2016
October 24-26, 2016
conferenceseries.com
Toxicology & Applied Pharmacology
October 24-26, 2016 Rome, Italy
7th Euro-Global Summit on
Kidney cell assays for in vitro safety profiling of single stranded oligonucleotides
Marcel Gubler
F Hoffmann-La Roche Ltd, Switzerland
C hronic treatment of patients with classical low molecular weight drugs like aminoglycoside antibiotics, antivirals
and immune-suppressants are known to induce kidney toxicities. Particularly molecules with high renal clearance
can accumulate in proximal tubule epithelial cells (PTECs) of the kidney cortex where high tissue concentrations induce
damage to tubular structures and may lead to loss of organ function. Similar toxicities have also been observed with other
drug modalities such as for example some single stranded oligonucleotides (SSOs). SSOs represent a class of novel drugs to
modulate gene expression in many different diseases for which there is no adequate treatment currently available. In order to
secure development of renal safe drugs, we have established assays with animal and human primary as well as immortalized
PTECs for profiling of nephrotoxic reference compounds side-by-side with SSOs that had previously been tested in rats for
signs of organ damage. Using assays of cell function, viability, and death, we have been able to clearly discriminate safe from
toxic molecules. Overall, the observed effects were similar across PTECs derived from animals and humans and correlated
with the in vivo findings for the molecules tested in rats. Thus, we believe that our cellular assays will be useful for rapid in vitro
profiling of SSOs for selection of safe compounds on human cells prior to clinical testing.
Biography
Marcel Gubler received his PhD in Life Sciences at the Federal Institute of Technology (Zürich, Switzerland) in 1988, followed by 2-years Post-doctoral Fellowship
at the Massachusetts Institute of Technology (Cambridge, MA). Subsequently, he joined Preclinical Research at F. Hoffmann-La Roche Ltd (Basel, Switzerland),
where he worked on novel targets for antibacterial therapies. In 2000, he changed to the Department of Metabolic Diseases to focus on drug treatments for obesity,
diabetes and renal diseases. Since 2014, he has been investigating mechanisms of renal toxicity of different drug modalities in the Department of Drug Disposition
and Safety, F. Hoffmann-La Roche Ltd.
Marcel Gubler, J Clin Toxicol 2016, 6:6(Suppl)