Liver involvement in hereditary lysozyme (ALys) amyloidosis: dissecting molecular mechanisms of disease (The LIALA study)

Hereditary lysozyme amyloidosis (ALys) is a very rare genetic disease where a faulty gene termed LYZ causes a protein called lysozyme to misfold and build up in the body, especially in the gut and liver. This can lead to serious complications, like life-threatening liver damage. The LIALA project, a teamwork effort between the University of Milan and the Amyloidosis Center in Pavia, aims to understand how this disease works, focusing on a specific genetic change called W82R, and find new ways to diagnose and treat it. The project has three main goals: 1) Study the W82R protein and harmful protein aggregates from patients using advanced microscopy and analysis tools, while also searching for drugs that can stop these aggregates from forming; 2) Test how the W82R protein damages liver cells to identify the pathogenic mechanisms and to find tools (biomarkers) that could help to diagnose the disease; 3) Use information from the largest group of ALys patients, all with the same genetic change and from one area in Italy, to better understand the disease, improve its detection, and validate the biomarkers. Experts from Milan and Turin add know-how on liver health and tissue analysis. LIALA tackles a critical need for a poorly understood, deadly disease with no current treatments. By combining cutting-edge science, patient data, and existing drugs, it offers hope for new diagnostic and therapeutic tools and supports Fondazione Telethon’s goal of finding cures for rare genetic diseases, potentially also helping other similar conditions.