Target Identification for RDS in Adults: RAGE

Poor validation of drug targets has been linked to costly clinical failures and low drug approval rates.¹ Identifying promising therapeutic targets is therefore crucial in the management of complex diseases, such as Respiratory Distress Syndrome (RDS). In this use case, AGER – which encodes for RAGE -was identified as a potential target for RDS in adults.

RDS is a severe pulmonary condition caused by insufficient surfactant production, primarily affecting lung function in premature infants. In the U.S., up to 30,000 newborns are estimated to be affected by RDS each year.² Adults can also develop Acute RDS (ARDS), particularly those with pre-existing conditions such as COPD.

Neonatal RDS is primarily caused by the immaturity of the lungs, while ARDS in adults typically arises from pre-existing lung conditions. For infants, surfactant therapy and ventilation are the primary interventions. In contrast, adults require tailored treatments addressing the causal conditions, fluid balance, and oxygen therapy.

Target identification is pivotal for elucidating disease mechanisms and developing more effective treatments. This is particularly crucial for diseases, such as RDS, facilitating precision interventions from early detection to tailored treatments. Causaly can expedite this process by enabling users to rapidly identify and explore evidence for target-disease associations.

Harnessing the power of Causaly has enabled navigation of the intricate landscape of RDS in adults. Over 1000 targets associated with RDS in adults were identified. Almost 50 of these have been reported on the ClinicalTrials.gov website, and over 200 are reported in clinical trials mapped from any Causaly data source. In the last 5 years, approximately 150 targets for RDS have been reported in clinical trial publications. Among these, AGER was selected as an emerging target of interest.

The AGER gene encodes for the RAGE  (Receptor for Advanced Glycosylation End-Products), a cell surface receptor primarily found in alveolar epithelium, which is upregulated in lung epithelial cells in ARDS.³ This gene has also been linked to COVID-19 severity.⁴

Research has shown a correlation between RAGE plasma concentrations and the risk of ARDS.⁵ A recent study highlighted the role of RAGE as an airspace biomarker associated with increased lung edema in ARDS patients.⁶ Given its role in RDS disease severity, targeting RAGE could be a promising avenue for developing more effective treatments for ARDS in adults.

In conclusion, identifying therapeutic targets is crucial in managing complex conditions like RDS. Understanding these targets provides insights into disease mechanisms and can guide personalized treatments. Causaly can expedite this process, paving the way for precision medicine and improved patient outcomes.