Zonal Guided Liver Testing for liver disease diagnosis and stratification

Descripción del proyecto

Prueba transcriptómica para el diagnóstico de las enfermedades hepáticas

La esteatohepatitis asociada a disfunción metabólica (EADM) es una enfermedad hepática crónica. Identificar a los pacientes de alto riesgo puede optimizar los recursos. La EADM comienza en los hepatocitos pericentrales y se evalúa mediante perfiles de ARN libre de células (cfRNA, por sus siglas en inglés), con patrones de genes que ayudan a la estratificación del tratamiento. Financiado por el Consejo Europeo de Investigación, el equipo del proyecto ZONESHED validará una prueba transcriptómica para diagnosticar la EADM utilizando cfRNA y biomarcadores de hepatocitos zonados con un algoritmo de aprendizaje automático. Esta prueba mejorará el diagnóstico de la EADM, reducirá los costes sanitarios y mejorará la evolución de los pacientes mediante intervenciones personalizadas. Para comercializar el kit de PCR digital de gotitas (ddPCR) de cfRNA y el clasificador ML de daño zonal, en ZONESHED se analizará el mercado del diagnóstico de enfermedades hepáticas, se colaborará con las partes interesadas del sector y se desarrollará un plan de comercialización.

Objetivo

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is emerging as the leading chronic liver disease worldwide. Identifying MASLD patients that are at higher risk of rapid progression is an outstanding challenge, but it would enable focusing resources on the patients with high risk while saving un-necessary costly liver function tests and biopsies for the majority of patients. MASLD progression is influenced by the liver's spatial heterogeneity, where variable gene expression along the porto-central axes of its lobules leads to the disease starting in pericentral hepatocytes and spreading portally, with greater portal involvement indicating more advanced stages. As hepatocytes die, they shed their content into the blood stream, enabling capturing a snapshot of liver turnover patterns by transcriptomically profiling cell free RNA (cfRNA). During my ERC-COG, I resolved the genome wide zonation patterns of all hepatocyte genes, allowing to determine the zone of damage and stratify patients for early follow-up and treatment. In this PoC, I will validate a targeted transcriptomic test of cfRNA for MASLD diagnosing, consisting of zonated hepatocyte biomarkers and an associated machine learning (ML) algorithm. The anticipated outcome is a significant improvement in MASLD diagnosis, reducing healthcare costs, and improving patient outcomes by tailoring interventions based on precise molecular insights. To pave the way for commercialization of our cfRNA droplet digital PCR (ddPCR) kit and associated zonal damage ML classifier, I will explore the liver disease diagnosis market and value chain, identify and engage with relevant industry players and set up a commercialization plan with the aim of positioning our innovation as the new standard for diagnosing and managing MASLD patients.