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Preclinical Research - Articles and news items


Ensuring patient safety during clinical trials; translation to preclinical drug discovery

Contract Research, Issue 4 2012 / 3 September 2012 / David Cook & James Milligan, AstraZeneca

Ensuring patient safety during clinical trials is of paramount consideration with stringent monitoring built into trials (and beyond) and the design and interpretation of safety outcomes subject to a large amount of regulation. As a result, it is rare for clinical trials to produce extreme adverse drug reactions but it is also quite common for new medicines to fail in clinical testing due to unacceptable patient safety within a given indication. This is because once a new drug reaches clinical testing, its safety profile is already ‘locked in’, and clinical testing can only discover issues that already exist. The ideal way to ensure the safety of patients is to only progress new medicines into clinical testing which do not have unacceptable safety or tolerability issues. However, to reach this ideal means using learning in the clinic to influence design and development in the laboratory. In this short article, we discuss the practical challenges in doing this and in ‘translating’ patient safety observations such that they can impact on drug design and early development…

MRI in drug discovery

Issue 1 2012, Magnetic Resonance Imaging / 28 February 2012 / Peter R. Allegrini, Novartis Institutes for BioMedical Research

MRI is widely used for clinical diagnosis as well as in research areas such as preclinical drug discovery, clinical development and also in therapy monitoring. MRI allows non-invasive acquisition of tomographic images of soft tissue with high resolution and contrast. Furthermore, its ability to assess organ function in a broad sense renders this technique to a versatile tool to answer specific scientific questions such as drug actions in disease models. Imaging of patho-physiological mechanisms and molecular processes are primarily in the focus of MRI in drug research. Finally, MRI is translational and has thus the potential to bridge the gap between preclinical research on one hand and clinical development or therapy monitoring on the other.

The magnetic moment of some atomic nuclei and with this, nuclear magnetic resonance (NMR), the basis of Magnetic Resonance Imaging (MRI), was predicted in the 1920s by Wolfgang Pauli and successfully demonstrated by Felix Bloch and Edward Purcell in 1946. With the detection of the chemical shift, the technique developed to a powerful analytical method for elucidation of chemical structures. Only decades later, in 1973, Paul Lauterbur published the first image based on NMR signal1. The breakthrough of MRI came with the intro – duction of the gradient based imaging techniques shortly thereafter as developed by Sir Peter Mansfield2. All these persons were later honoured for their contributions to NMR and MRI with the Nobel Prize.


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