NDLI: Steps to Translate Preconditioning from Basic Research to the Clinic

Content Provider	Springer Nature Link
Author	Bahjat, Frances R. Gesuete, Raffaella Stenzel Poore, Mary P.
Copyright Year	2012
Abstract	Efforts to treat cardiovascular and cerebrovascular diseases often focus on the mitigation of ischemia–reperfusion (I/R) injury. Many treatments or “preconditioners” are known to provide substantial protection against I/R injury when administered prior to the event. Brief periods of ischemia itself have been validated as a means to achieve neuroprotection in many experimental disease settings, in multiple organ systems, and in multiple species suggesting a common pathway leading to tolerance. In addition, pharmacological agents that act as potent preconditioners have been described. Experimental induction of neuroprotection using these various preconditioning paradigms has provided a unique window into the brain's endogenous protective mechanisms. Moreover, preconditioning agents themselves hold significant promise as clinical-stage therapies for prevention of I/R injury. The aim of this article is to explore several key steps involved in the preclinical validation of preconditioning agents prior to the conduct of clinical studies in humans. Drug development is difficult, expensive, and relies on multifactorial analysis of data from diverse disciplines. Importantly, there is no single path for the preclinical development of a novel therapeutic and no proven strategy to ensure success in clinical translation. Rather, the conduct of a diverse array of robust preclinical studies reduces the risk of clinical failure by varying degrees depending upon the relevance of preclinical models and drug pharmacology to humans. A strong sense of urgency and high tolerance of failure are often required to achieve success in the development of novel treatment paradigms for complex human conditions.
Starting Page	89
Ending Page	103
Page Count	15
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	4
Issue Number	1
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2012-11-02
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Preconditioning Stroke Cardiovascular disease Therapeutic Animal models of stroke Nonhuman primate Mouse MCAO Occlusion Toll-like receptors Ischemia Repercussion Brain injury Ischemic brain injury Cerebral ischemia Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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