The present invention proposes the use of soluble P2X7 receptor (sP2X7R) as a sensitive and specific upstream biomarker for the early diagnosis of neonatal sepsis-associated encephalopathy (NSAE). Preclinical studies by the group have demonstrated that systemic activation of P2X7R using an agonist in neonatal mice born to Group B Streptococcus-infected dams improved survival, clinical, neurodevelopmental, and long-term behavioural outcomes. These findings support the relevance of the P2X7R pathway in NSAE and suggest the potential of sP2X7R as an upstream biomarker of this pathology. Unlike other conventional markers, such as neuron-specific enolase (NSE) or S100β, which reflect downstream neuronal damage and have an inconsistent performance, sP2X7R enables an earlier detection during a reversible stage of brain injury, increasing the chances of preventing lifelong disability. The serum levels of sP2X7R could be evaluated using a small volume of neonatal blood. Hence, this minimally-invasive test could be turned into a scalable, point-of-care diagnostic test, with advantages over other costly, impractical techniques like magnetic resonance imaging or electroencephalogram.
Current diagnosis of NSAE is often delayed and based on indirect signs (such as clinical observation, neuroimaging or electrophysiology), which are either nonspecific, retrospective, or logistically inaccessible in the acute setting. This diagnostic delays prevent early neuroprotective interventions and increases the risk of irreversible brain injury and long-term neurodevelopmental disability.
The sP2X7R is a specific and sensitive upstream marker that would allow for early detection of NSAE, during a reversible stage of brain injury. It is a minimally invasive test (requiring only a small blood sample from the newborn), which has the potential to be adapted into a scalable, real-time, point-of-care diagnostic.
Biomarker-based diagnostic test; Clinical diagnostic service for hospital laboratories.
