Phase II anti-inflammatory and immune-modulating drugs for acute ischaemic stroke.
BACKGROUND
Stroke is the second leading cause of death worldwide and the leading cause of adult neurological disability. Despite advances in stroke unit care, and increasing use of thrombolysis, there remains an urgent need for safe and effective treatments for acute ischaemic stroke. However, this is against a backdrop of multiple failures in translational drug development. Cerebral ischaemia initiates a complex cascade of immune and inflammatory pathways in the brain microvasculature and periphery, which contribute to the evolution of cerebral injury, resolution and repair. Targeting specific inflammatory or immune pathways, therefore, represents an attractive treatment strategy in acute ischaemic stroke. Although anti-inflammatory drugs have already failed in clinical trial development, several are currently at the Phase II developmental stage.


METHODS
The authors highlight several candidate drugs, which modulate a range of inflammatory and immune pathways, and have been investigated in pre-clinical and Phase II studies to date.


CONCLUSIONS
Drugs targeting inflammatory and immune pathways offer theoretical advantages including potentially longer therapeutic time windows and effects complementary to thrombolysis (ameliorating reperfusion injury). Fundamental changes in the approach to pre-clinical and clinical drug development are required to facilitate successful translation of promising candidate drugs into clinical practice.
Greater Manchester Comprehensive Stroke Centre, Department of Medical Neurosciences, Salford Royal Foundation Trust , Salford , UK.
Craig J
CJ
Smith
Adam
A
Denes
Pippa J
PJ
Tyrrell
Mario
M
Di Napoli
D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D057170:Translational Research, Biomedical
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors
acute ischaemic stroke; anti-inflammatory; cerebral ischaemia; inflammation; translational research