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Controversies in Neurology
April 2001

Inflammation and StrokeBenefits Without Harm?

Author Affiliations

From the Department of Cardiovascular Sciences, Dupont Pharmaceuticals Co, Wilmington, Del.

 

JOHN N.WHITAKERMD

Arch Neurol. 2001;58(4):672-674. doi:10.1001/archneur.58.4.672

AT THE onset of the 21st century, stroke is the third-leading cause of death in most developed countries and the primary cardiovascular cause of death in Japan and China.1 The health burden of the disease is staggering as loss of a productive life inflicts a heavy toll on patients, families, and society. Yet this disease has no effective therapy beyond a limited group of patients (5%) who are treated with thrombolytics, which have significant adverse effects. This situation prevails despite intense research efforts and numerous clinical trials that have attempted to develop drugs to reduce morbidity and mortality from stroke. So far, drug development efforts have targeted modulators of ion channels (Ca2+and Na+), scavengers of oxygen radicals, and antagonists of excitotoxic neurotransmitters (primarily glutamate and glycine receptors). However, clinical trials with modulators of these targets have failed so far because of lack of efficacy, adverse effects, or other developmental difficulties. Debate on the reasons for this grim reality has sprung up in recent meetings, with finger-pointing about major possible causes of failure including incorrect animal models, misidentified mechanisms of action, poor clinical designs, inadequate timing of treatment, and other variables.

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