Drug safety studies

The development of totally new classes of drugs like therapeutical antibodies, gene therapy and small molecules challenges the traditional way of drug safety testings. Furthermore, the mechanisms that make a drug effective are often not fully understood. Pre-clinical studies are mostly limited to assess toxicity and bioavailability and to confirm that the tested compound has the expected effect. Unexpected negative but also positive side effects of a drug are frequently only revealed after years of application in clinical practice.
Modern molecular biology methods like gene arrays are helpful tools to elucidate the impact of a substance on cell populations or tissues. Changes in the gene expression profile after treatment are detectable, and thereby the molecular mechanisms of known drug actions can be explained or even novel actions of a drug can be found (Fig 3)).
Drug safety studies in the Center of Experimental Rheumatology are conducted in vitro by incubating a distinct target cell population with the respective drug or in vivo by collection tissue or blood samples from patients before and after treatment. In both cases, important information about modifications on the cellular basis are gained and help to improve the development of safe and specific drugs.

Publications

Ospelt C, Neidhart M, Gay RE, Gay S. Gene analysis for exploring the effects of drugs in rheumatoid arthritis. Arthritis Rheum 2005, 52:2248-56.

Ospelt C, Gay S. Safety concerns on the development of novel therapeutic drugs. Arthritis Res Ther 2006, 8:112.

Ospelt C, Kurowska-Stolarska M, Neidhart M, Michel BA, Gay RE, Laufer S, Gay S. The dual inhibitor of lipoxygenase and cyclooxygenase ML3000 decreases the expression of CXCR3 ligands. Ann Rheum Dis 2007 [Epub ahead of print]

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