Volume 6 Issue 8, August 2007

The possibility of more widespread application of 'personalized medicine', in which therapy is tailored to factors such as an individual's genetic make-up, has been on the horizon for years, but so far, translation of this concept to clinical practice has been limited. What might it take to change this situation?

Embryonic stem cells (ESCs) can be used as a source of cellular models for a wide range of adult differentiated cells, providing that reliable differentiation protocols are established. Here, Pouton and Haynes discuss challenges and opportunities regarding the use of ESC-derived models for drug discovery.

Hypertrophy of heart cells stimulated by pathological stress from cardiovascular disease increases the risk of morbidity and mortality, and inhibition of such hypertrophy is attracting increasing attention as a therapeutic strategy. McKinsey and Kass provide a comprehensive summary of small-molecule inhibitors of cardiac hypertrophy and intracellular signalling pathways that offer further promising therapeutic targets.

Toxicity is a leading cause of attrition at all stages of the drug development process. In their Review, Kramer and colleagues discuss how the early application of preclinical safety assessment can aid the design of safer pharmaceutical lead candidates.

In vitromodels of the blood–brain barrier (BBB) allow predictions of brain uptake for candidate drugs. Providing guidance through the plethora of BBB models, the authors discuss the pros and cons of different models, and their applications at various stages of drug discovery and development.

Peroxynitrite — the product of the reaction of nitric oxide with superoxide radical — is a potent inducer of cell death. Szabó and colleagues review the biochemistry and pathophysiology of peroxynitrite and discuss pharmacological strategies to attenuate its toxic effects, which have lead to potential drug development candidates for cardiovascular, inflammatory and neurodegenerative diseases.