Reperfusion injury is referred to as the tissue damage caused due to absence of blood supply or lack of oxygen such as damage to brain after stroke or heart post episodes of ischemia. Such kind of restoration of blood supply results into inflammation and oxidative damage through the induction of oxidative stress rather than normal functioning. Confined infarct size and reduced mortality can be achieved by prompt restoration of blood supply to myocardium. However, this restoration is also known to result in the cardiac damage and eventually reperfusion injury. A delay in reperfusion therapy has been attributed for such damage.
Reperfusion of ischemic tissue is often associated with microvascular injury. The duration for which a tissue can survive deprived of oxygen varies, but eventually the tissue is rendered necrotic. The blood supply restoration usually minimizes the damage, but reperfusion of tissue post thrombolytic procedures demonstrated that the extent of injury often increased on restoration of the blood supply. The studies have also attributed this reperfusion injury, to the activity of free radicals.
The global reperfusion injury market can be segmented based on therapy type, injury type and geography. Drugs used for treating reperfusion injury are classified on the basis of mode of action, target site, route of administration and molecule type. Geographically, the global reperfusion injury market can be categorized into four major regions namely, North America, Europe, Asia-Pacific and Rest of the World. Primary percutaneous coronary intervention (PCI) and thrombolysis, form the primary reperfusion therapies and are often used for treating acute coronary syndromes.
Allopurinol, one of the drugs in clinical trials helps inhibit production of free radicals thereby known to reduce the size of infarct. However the drug has not been universally successful. An enzyme called recombinant superoxide dismutase has been under investigation as free radical scavenger that detoxifies oxygen. Various other drug molecules in clinical trials include cyclosporine, MTP-131, bucillamine, recombinant proteins, type 5 adenylyl cyclase inhibitors, and synthetic peptides amongst others. Agents that specifically target proteins, transcription factors or ion channels, including PPAR, PKC agonists/antagonists, Phosphodiesterase-5 inhibitors, the ATP-dependent potassium channel and 3-Hydroxy-3-methyl glutaryl coenzyme A reductase are also promising.
However, currently no agent has been clinically approved for treatment of reperfusion injury. Studies demonstrating success in the clinical use have been disappointing for last few years though successful results have been observed on animals. The unclear solutions and lesser potential therapies that limit the free radicals generation on reperfusion are also under investigation in several clinical trials. New avenues for investigation are recently opened due to studies demonstrating involvement of inflammatory cytokines and their effects on neutrophiles.
Additionally, a combination of better techniques for rapid reperfusion and use of neutrophil inhibitors and anti-oxidants will help in reduction of the enormous cost associated with the clinical trials for treatment of reperfusion injury. Other options under study for treatment of reperfusion injury include hypothermia treatment, post conditioning such as mechanical and pharmacologic have shown success in few patients.
Larger experiments exploring the potential of various therapeutic options in order to influence clinically relevant endpoints are yet awaited for options which are currently insufficiently demonstrated in clinical use of these reperfusion injuries.
Apeptico Forschung und Entwicklung GmbH, Eustralis Pharmaceuticals Ltd., NeuroVive Pharmaceutical AB, Nyken BV, Stealth Peptides, Inc., Scynexis, Inc., and Vasade Biosciences, Inc. are some of the key players contributing to the global reperfusion injury market.
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