Nature reviews. Drug discovery
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Nat Rev Drug Discov · Feb 2006
ReviewParadigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond.
Neuroprotective drugs tested in clinical trials, particularly those that block N-methyl-D-aspartate-sensitive glutamate receptors (NMDARs), have failed miserably in large part because of intolerable side effects. However, one such drug, memantine, was recently approved by the European Union and the US FDA for the treatment of dementia following our group's discovery of its clinically tolerated mechanism of action. Here, we review the molecular basis for memantine efficacy in neurological diseases that are mediated, at least in part, by overactivation of NMDARs, producing excessive Ca(2+) influx through the receptor's associated ion channel and consequent free-radical formation.
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Nat Rev Drug Discov · Nov 2005
ReviewOutlook: finding improved medicines: the role of academic-industrial collaboration.
This paper reviews models of academic-pharmaceutical industry collaboration and debates the value of such partnerships so that those contemplating an alliance can reflect a priori on the purpose, nature and process that will provide a constructive outcome. The scope is confined to the biomedical discipline, because collaborations in other fields, such as physics and engineering, have not suffered as a result of the concerns associated with biomedicine.
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Sepsis is a state of disrupted inflammatory homeostasis that is often initiated by infection. The development and progression of sepsis is multi-factorial, and affects the cardiovascular, immunological and endocrine systems of the body. ⋯ However, demonstrated benefit from a therapeutic agent in animal models has rarely been translated into success in human clinical trials. This review summarizes the common animal sepsis models and highlights how results of recent human clinical trials might affect their use.
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Cetuximab (Erbitux; ImClone Systems/Bristol-Myers Squibb) is a monoclonal antibody that binds to the epidermal growth factor receptor, which is important in the growth of many cancers. In February 2004, it was granted accelerated approval by the US FDA for the treatment of metastatic colorectal cancer on the basis of tumour response rates in Phase II trials.
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Oncology, as a therapeutic area, is characterized by a desperate medical need for new drugs; the use of drugs that kill cells and which are consequently often toxic; and rates of failure in expensive Phase III trials that eclipse many other disease areas. The poor performance of most investigational cancer drugs implies that the standard preclinical disease models are faulty or, at least, improperly used. Some studies, however, support the view that cancer models can be highly effective, but only when selected and interpreted with care.