Pulmonary hypertension biomarker

Abstract

Pulmonary hypertension is a progressive disease of various origins that is associated with vascular remodelling and results in right heart dysfunction. Accumulating evidence indicates important roles of immune cells and inflammatory chemokines in the pathogenesis and progression of pulmonary hypertension. We have identified CCL21 as anti-remodelling efficacy biomarker for pulmonary hypertension. CCL21 was found to be highly sensitive and specific in discriminating pulmonary hypertension patients from matched controls. CCL21 was upregulated in pulmonary hypertension and down-regulated with treatment with an anti-remodelling agent.

Description

FIELD OF THE INVENTION[0001]The invention is in the field of biomarkers in respiratory disease. In particular, it relates to the use of CCL21 expression as a biomarker for pulmonary hypertension.BACKGROUND OF THE INVENTION[0002]Pulmonary hypertension is a progressive disease of various origins that is associated with a poor prognosis and results in right heart dysfunction. In all its variant presentations, this disease is estimated to affect up to 100 million people worldwide1. According to the current classification of pulmonary hypertension, which was agreed upon at the 4th World Symposium on Pulmonary Hypertension in 2008, five categories of chronic pulmonary hypertension exist.[0003]Pulmonary hypertension (PH) is defined as a mean rise in pulmonary arterial pressure >25 mmHg at rest (>30 mmHg following exercise). Group 1 PH can be further subdivided into diseases where increased pulmonary vascular resistance is due to pre-capillary micro-angiopathy (diagnosed as a pre-capi...

AI Technical Summary

Benefits of technology

The patent text describes a new biomarker called CCL21 that can be used to diagnose and treat pulmonary hypertension. The invention provides a method for determining if a person has pulmonary hypertension by measuring the level of CCL21 expression and / or CCL21 protein in a biological sample from the person. The method can also be used to predict which patients will respond to treatment with a pulmonary hypertension antagonist. The patent also describes a kit for detecting CCL21 expression and / or CCL21 protein in a biological sample. Overall, the invention provides a reliable and sensitive tool for diagnosing and treating pulmonary hypertension.

Problems solved by technology

Pulmonary hypertension is a progressive disease of various origins that is associated with a poor prognosis and results in right heart dysfunction.

Despite advances in understanding of the underlying pathobiology of pulmonary hypertension and some improvements in diagnosis and development of novel therapeutics, there is still significant unmet medical need and unacceptable rates of morbidity and mortality across the spectrum of pulmonary hypertension.

However, they all are characterized by excessive pulmonary vasoconstriction and abnormal vascular remodelling unique plexiform lesions.

Vascular remodelling leads to a chronic elevation of pulmonary vascular resistance, right heart failure and death.

However, BNP or NT-proBNP, are markers of myocardial strain, excessive stretching of the heart, and increased heart rate and do not directly reflect changes in distal pulmonary arteries in the lung, which are responsible for driving pulmonary hypertension pathophysiology.

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