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Validation of microRNAs as novel diagnostic and therapeutic targets in ischaemic brain injury

RCSI StAR International PhD Programme Research Projects

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Dr S Pfeiffer Applications accepted all year round Self-Funded PhD Students Only

About the Project

Ischaemic stroke is a leading cause of death and most common cause of acquired major disability resulting from death of brain tissue and focal neurological deficits; however, despite decades of research, treatment options remain limited and the lack of therapeutic treatment strategies is a critical clinical problem. To this end, there is a need for biomarkers as clinically useful diagnostic and prognostic indicators for outcome in patients, improving functional recovery through individualised therapeutic strategies. Furthermore, such biomarkers have potential to be developed into neuroprotective agents aimed at rescuing ischaemic neurons from irreversible injury, widening the therapeutic window, improving neurological outcome and facilitating brain recovery.

Endogenous microRNAs (miRNA) are potent regulators of gene function elevated in a wide range of diseases, with crucial roles as regulators of signaling pathways involved in ischaemia-reperfusion injury. The complex nature of the ischaemic cascade has made identification of clinically useful biochemical markers of ischaemia challenging despite statistical associations with stroke and therefore targeting a single pathway may be ineffective. The roles played by miRNAs and their dysregulation in disease, particularly their ability to regulate multiple genes in similar pathways given the heterogeneity of stroke pathophysiology, combined with remarkable stability in biofluids and easy detection leave them uniquely poised as ideal biomarkers and therapeutic targets in many future clinical trials. Identification of a stable, endogenously expressed biomarker will be of significant clinical value in the development of a rapid blood test based on simple, cost-effective, near-patient technology, thereby contributing valuable and timely information necessary for prompt patient management decisions in the acute setting. Such information would aid in the choice of appropriate therapeutic intervention, treatment and secondary prevention and help with identifying timing of onset. Furthermore, identification of multi-targeting endogenously expressed biomarkers has significant potential for the development of neuroprotective agents, reducing stroke mortality rates.

The outcomes of this research will have significant potential for application and translation as effective and feasible interventions, substantially improving patient care and outcome.
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