Title:Oncostatin M: Risks and Benefits of a Novel Therapeutic Target for
Atherosclerosis
Volume: 23
Issue: 14
关键词:
onscoatin M, OSM，动脉粥样硬化，风险-优势分析，靶标安全性评估，风险评估。
摘要:
Background: Cardiovascular disease (CVD) is a leading cause of death worldwide. It is
predicted that approximately 23.6 million people will die from CVDs annually by 2030. Therefore,
there is a great need for an effective therapeutic approach to combat this disease. The European
Cardiovascular Target Discovery (CarTarDis) consortium identified Oncostatin M (OSM) as a potential
therapeutic target for atherosclerosis. The benefits of modulating OSM - an interleukin (IL)-6
family cytokine - have since been studied for multiple indications. However, as decades of high attrition
rates have stressed, the success of a drug target is determined by the fine balance between
benefits and the risk of adverse events. Safety issues should therefore not be overlooked.
Objective: In this review, a risk/benefit analysis is performed on OSM inhibition in the context of
atherosclerosis treatment. First, OSM signaling characteristics and its role in atherosclerosis are described.
Next, an overview of in vitro, in vivo, and clinical findings relating to both the benefits and
risks of modulating OSM in major organ systems is provided. Based on OSM’s biological function
and expression profile as well as drug intervention studies, safety concerns of inhibiting this target
have been identified, assessed, and ranked for the target population.
Conclusion: While OSM may be of therapeutic value in atherosclerosis, drug development should
also focus on de-risking the herein identified major safety concerns: tissue remodeling, angiogenesis,
bleeding, anemia, and NMDA- and glutamate-induced neurotoxicity. Close monitoring and/or
exclusion of patients with various comorbidities may be required for optimal therapeutic benefit.
