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Pegaptanib, an RNA aptamer that binds to vascular endothelial growth factor, was approved for the treatment of age-related macular degeneration in December 2004, becoming both the first approved aptamer therapeutic and the first anti-angiogenic agent for treating ocular disease.
Sánchez-Serrano discusses the story of the innovative anticancer drug bortezomib to dissect the key public-sector-private sector interactions that made the development of this drug successful despite many barriers, and considers the implications for improving translational research in general.
Excessive glutamate receptor activity, principally of theN-methyl-D-aspartate (NMDA) subtype, contributes to neuronal damage in a large number of neurologic disorders, including dementia. Until recently, however, NMDA receptor antagonists had all failed in clinical trials. Stuart Lipton reviews the mechanism of action that led to the clinical approval of the first NMDA receptor antagonist, memantine, which has become the newest and one of the best-selling drugs for Alzheimer's disease.
Targeting drugs specifically to tumour cells to improve efficacy and reduce toxicity is paramount to the future development of anti-cancer agents. Schrama and colleagues critically review current approaches to achieving this and the status of targeted treatments in development.
Bayesian statistical methods are being increasingly used in clinical research owing to the advantages they can offer compared with conventional approaches. Berry explains the underlying rationale, and discusses the potential of Bayesian trials to improve the effectiveness of drug development.
Cyclooxygenase-2-selective drugs were designed to be safer alternatives to traditional NSAIDs. However, concerns that they increase the risk of thrombotic events have led to the withdrawal of some of these drugs. Mitchell and Warner discuss their underlying mechanisms of actions.
Targeting the epigenetic changes that contribute to tumorigenesis has become an attractive therapeutic strategy. Yoo and Jones review the enzymes involved in epigenetic regulation that are emerging as targets and the numerous drug candidates that are currently being investigated.
Behavioural changes have a major impact on the quality of life of patients with neurodegenerative diseases. Cummings and Zhong discuss how new tools for studying behaviour and improved clinical trial methodologies are facilitating drug development for this large unmet medical need.
