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RNA interference therapy: a new solution for intracranial atherosclerosis?
Xiang-Yan Chen1, Tao Tang1, Ka-Sing Wong1
11 Departments of Medicine and Therapeutics, 2 Department of Obstetrics & Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Insights
Intracranial atherosclerotic stenosis (ICAS) increases stroke risk. Intraplaque hemorrhage in middle cerebral artery (MCA) stenosis, detected by HRMRI, indicates higher stroke risk and suggests targets for plaque stabilization therapies.
Area of Science:
- Neurology
- Cardiovascular Research
- Biomedical Imaging
Background:
- Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke globally.
- ICAS patients face a higher risk of recurrent stroke, even with medical treatment.
- Plaque characteristics, not just luminal stenosis, are linked to stroke risk.
Purpose of the Study:
- To investigate the association between intraplaque hemorrhage (IPH) in middle cerebral artery (MCA) stenosis and ischemic stroke.
- To explore novel therapeutic strategies targeting plaque stabilization in ICAS.
- To evaluate the potential of RNA interference (RNAi) therapy delivered by nanoparticles for imaging and treatment.
Main Methods:
- Utilized high-resolution magnetic resonance imaging (HRMRI) to assess MCA plaque morphology and components.
- Identified high signal on T1-weighted fat-suppressed images (HST1) as an indicator of IPH.
- Proposed RNA interference (RNAi) therapy combined with modified nanoparticles for targeted intervention.
Main Results:
- HRMRI revealed that HST1, indicative of IPH, is associated with ipsilateral brain infarction in MCA stenosis patients.
- Symptomatic MCA stenosis patients exhibit a higher prevalence of IPH and neovasculature.
- Nanoparticle-delivered RNAi therapy is hypothesized for in vivo imaging and targeted treatment.
Conclusions:
- Intraplaque hemorrhage in MCA stenosis is a significant marker for ischemic stroke risk.
- Targeting IPH and neovasculature presents a promising strategy for plaque stabilization in ICAS.
- Nanotechnology offers potential for advanced diagnostics and therapeutics in atherosclerosis treatment.
Abstract:
Intracranial atherosclerotic stenosis (ICAS) of a major intracranial artery, especially middle cerebral artery (MCA), is reported to be one leading cause of ischemic stroke throughout the world. Compared with other stroke subtypes, ICAS is associated with a higher risk of recurrent stroke despite aggressive medical therapy. Increased understanding of the pathophysiology of ICAS has highlighted several possible targets for therapeutic interventions. Both luminal stenosis and plaque components of ICAS have been found to be associated with ischemic stroke based a post-mortem study. Recent application of high-resolution magnetic resonance imaging (HRMRI) in evaluating ICAS provides new insight into the vascular biology of plaque morphology and component. High signal on T1-weighted fat-suppressed images (HST1) within MCA plaque of HRMRI, highly suggested of fresh or recent intraplaque hemorrhage, has been found to be associated with ipsilateral brain infarction. Thus, the higher prevalence of intraplaque hemorrhage and neovasculature in symptomatic patients with MCA stenosis may provide a potential target for plaque stabilization. We hypothesize that RNA interference (RNAi) therapy delivered by modified nanoparticles may achieve in vivo biomedical imaging and targeted therapy. With the rapid developments in studies about therapeutic and diagnostic nanomaterials, future studies further exploring the molecular biology of atherosclerosis may provide more drug targets for plaque stabilization.
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