A model score calculated from levels of circulating plasma proteins for the diagnosis, prognosis, and treatment optimisation of Pulmonary Arterial Hypertension.
Proposed use
- Point of Care test: Pulmonary Arterial Hypertension diagnosis/prognosis – risk stratification
- Pulmonary Arterial Hypertension treatment response and optimisation monitoring/evaluation
Problem addressed
Pulmonary arterial hypertension (PAH) is a rare condition that continues to be associated with a high morbidity and mortality burden. Because patients with PAH have very variable responses to standard therapies which is difficult to predict, as well as monitoring the effectiveness of such therapies. The N-terminal pro-brain natriuretic peptide (NT-proBNP), is a biomarker of cardiac origin already used to risk stratify patients with pulmonary arterial hypertension (PAH) but has its limitations, including poor sensitivity to early vascular pathology. The plasma proteome can inform prognosis beyond established factors in PAH and may provide a more sensitive and quicker measure of therapeutic response.
Technology overview
An aptamer-based assay targeting over 4000 proteins was used to measure plasma proteins in two idiopathic/heritable/drug-induced-PAH patient cohorts.
Discovery-validation survival analyses permitted identification of approximatively 30 proteins associated with PAH that could reproducibly inform prognosis independent of established prognostic factors NT-proBNP and 6-MWD.
From the 30 proteins a weighted combination score of 6 biomarker proteins (selected by LASSO) was developed and validated at baseline and follow-up study.
The value of this score permits, independently of established clinical targets, discrimination between:
- Low/intermediate/high risk of PAH progression/death
- Response to therapy
- Development of PAH in at-risk individuals
Benefits
- Accessible point-of-care test for earlier diagnosis of PAH.
- Non-invasive test
- Easy to interpret single measurement
- More sensitive measure of risk / therapeutic response / disease progression
- Complements established clinical measures / risk algorithms
- Reflects underlying pathobiology rather than late-stage heart failure
Development Stage
- TRL 2/3
- Model developed using SomaLogic SomaScan v4 data in UK PAH Cohort
- Model validated in external cohort from Paris, France
- 4/6 proteins validated by commercial ELISA measurements
Intellectual property information
A PCT Patent application has been published (WO2022/079448), covering the PROPHSY score and associated biomarkers. A national patent application has also been filed at the EPO.
