Stroke genetics and how it Informs novel drug discovery

ABSTRACT

Introduction

Stroke is one of the main causes of death and disability worldwide. Nevertheless, despite the global burden of this disease, our understanding is limited and there is still a lack of highly efficient etiopathology-based treatment. It is partly due to the complexity and heterogenicity of the disease. It is estimated that around one-third of ischemic stroke is heritable, emphasizing the importance of genetic factors identification and targeting for therapeutic purposes.

Areas covered

In this review, the authors provide an overview of the current knowledge of stroke genetics and its value in diagnostics, personalized treatment, and prognostication.

Expert opinion

As the scale of genetic testing increases and the cost decreases, integration of genetic data into clinical practice is inevitable, enabling assessing individual risk, providing personalized prognostic models and identifying new therapeutic targets and biomarkers. Although expanding stroke genetics data provides different diagnostics and treatment perspectives, there are some limitations and challenges to face. One of them is the threat of health disparities as non-European populations are underrepresented in genetic datasets. Finally, a deeper understanding of underlying mechanisms of potential targets is still lacking, delaying the application of novel therapies into routine clinical practice.

KEYWORDS:

• Stroke
• genetics
• novel drugs
• genome-wide association studies
• genetic risk score
• noncoding RNAs
• mendelian randomization
• omics

Article highlights

• Stroke is a multifactorial, heterogenic group of diseases, that share some common pathophysiological features, though individual differences complicate the discovery of the new potent drugs.

• Growing evidence suggest that distinction between monogenic and polygenic stroke is less evident than it was thought.

• Polygenic risk score together with clinical factors may be a useful tool to assess individual risk and provide appropriate timely prevention, such as more aggressive risk factor modification.

• With the prompt expansion and availability of genetic data resources, the potential of Mendelian randomization to discover new drug targets is promising.

• Further research with murine models in stroke genetics and its translation to humans is highly important in order to understand the mechanisms behind stroke genetics for a more personalized and aggressive treatment approach.

• Genetic information serves for pharmacogenetics, individual risk assessment, timely prevention, and generation of new targets for treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.