Drug discovery today
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Drug discovery today · Dec 2008
ReviewModern multiple sclerosis treatment - what is approved, what is on the horizon.
In the mid-1990s, the implementation of the immunomodulatory drugs interferon-beta and glatiramer acetate offered the first evidence-based treatment option for multiple sclerosis (MS). These new drugs were beneficial in a huge number of MS patients worldwide, leading to a delay in disease-related disability. ⋯ It will presumably be followed by several other more specific, more effective and more comfortable therapies within the next few years. Here, we will show the current MS treatment options as well as recent progress in the field, and we will introduce the potential new treatment options for future MS therapy.
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Drug discovery today · Dec 2008
ReviewThe targeted delivery of cancer drugs across the blood-brain barrier: chemical modifications of drugs or drug-nanoparticles?
One of the most challenging problems, if not the most challenging, in drug development is not to develop drugs to treat diseases of the central nervous system (CNS), but to manage to distribute them to the CNS across the blood-brain barrier (BBB) using transvascular routes following intravenous administration. The development of BBB targeting technologies is a very active field of research and development. One goal is to develop chemically modified derivatives of drugs or chemically modified nanoparticulate vectors of drugs, capable of crossing biological barriers, in particular the BBB. This manuscript will review the approaches that have been explored to achieve these goals, using chemical functionalization of drugs or of drug vector systems and endogenous transporters at the BBB.
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Since the demonstration of RNA interference (RNAi) in mammalian cells, considerable research and financial effort has gone towards implementing RNAi as a viable therapeutic platform. RNAi is, without doubt, the most promising strategy for the treatment of human genetic disorders. Because many of the targets proposed for RNAi therapy require chronic treatment, researchers agree that the emphasis must now be placed on the safe and long-term application of RNAi drugs to reap the benefits at last.
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Drug discovery today · Jun 2008
ReviewUse of genetically modified rat models for translational medicine.
Because of its relevance to human physiology, the rat may provide highly predictable models for the pharmaceutical industry. Until recently, the lack of efficient tools to manipulate the rat genome has drastically limited the use of this research model. ⋯ This review presents a state-of-the-art transgenic technologies in the rat and their application to biomedical research. Novel technologies enabling the faithful expression of human genes in rats are focussed on specifically.
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Drug discovery today · Mar 2008
ReviewNew insights into the causes and therapy of cerebral vasospasm following subarachnoid hemorrhage.
Cerebral vasospasm lingers as the leading preventable cause of death and disability in patients who experience aneurysmal subarachnoid hemorrhage. Despite the potentially devastating consequences of cerebral vasospasm, the mechanisms behind it are incompletely understood. Nitric oxide, endothelin-1, bilirubin oxidation products and inflammation appear to figure prominently in its pathogenesis. Therapies directed at many of these mechanisms are currently under investigation and hold significant promise for an ultimate solution to this substantial problem.