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Published on: February 20, 2019
Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis
Robin P Choudhury1, Rupen Hargreaves2, Jason Chai1
1Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Abstract:
The current generation of highly successful atherosclerosis treatments, such as low-density lipoprotein (LDL)-cholesterol reduction, blood pressure management, and smoking cessation, has largely focused on ameliorating factors perceived to drive incident disease and its complications. The adverse contributions of these factors have typically been identified through epidemiological studies. The therapeutic strategies that arose in response focused on risk factors for disease development and tended to overlook the fact that patients already have established disease, by the time of presentation. However, by capitalizing on contemporary biological knowledge and technologies, it is becoming increasingly possible to shift from a model based on population-derived risk factor management to next-generation treatments (including monoclonal antibodies, small interfering RNA [siRNA], mRNA, epigenetic reprogramming, and gene editing) for atherosclerosis that are tailored to patient-level disease processes, informed by mechanistic characterization, offer potential to reverse or regress disease, and incorporate systems-level interventions that extend beyond the atherosclerotic plaque.
Insights
Current atherosclerosis treatments manage risk factors but overlook established disease. Next-generation therapies offer personalized, mechanistic approaches to potentially reverse atherosclerosis progression.
Area of Science:
- Cardiovascular Medicine
- Translational Medicine
- Molecular Biology
Background:
- Current atherosclerosis treatments focus on population-derived risk factors like LDL-cholesterol, blood pressure, and smoking.
- These strategies primarily address disease development and complications, often neglecting patients with established atherosclerosis.
- Epidemiological studies have guided current risk factor management approaches.
Purpose of the Study:
- To transition from population-based risk factor management to patient-specific, mechanistic treatments for atherosclerosis.
- To explore next-generation therapeutic strategies capable of reversing or regressing established atherosclerotic disease.
- To incorporate systems-level interventions beyond the atherosclerotic plaque itself.
Main Methods:
- Leveraging contemporary biological knowledge and advanced technologies.
- Developing targeted therapies including monoclonal antibodies, small interfering RNA (siRNA), and mRNA.
- Exploring novel approaches such as epigenetic reprogramming and gene editing.
- Characterizing patient-level disease processes mechanistically.
Main Results:
- Emerging biological knowledge enables a shift towards personalized atherosclerosis treatments.
- Next-generation therapies show potential for disease reversal or regression.
- Systems-level interventions offer a broader therapeutic scope.
Conclusions:
- A paradigm shift is occurring in atherosclerosis treatment, moving towards precision medicine.
- Advanced biological insights and technologies are paving the way for novel therapeutic modalities.
- Future treatments will likely be tailored to individual patient disease processes, aiming for regression.
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