Tirzepatide Monotherapy Trial Initiated for Wolfram Syndrome Type 1 to Boost Insulin Production

Wolfram syndrome (WFS1) is a rare, inherited disorder characterized by early-onset diabetes, optic atrophy, deafness, and often diabetes insipidus, affecting approximately 0.2 in 10,000 people in the EU. Caused by mutations in the WFS1 gene, it leads to dysfunction of wolframin, a transmembrane glycoprotein crucial for endoplasmic reticulum (ER) stress regulation. Currently, there is no cure or treatment to halt disease progression. Repurposing drugs, particularly GLP-1 receptor agonists, has been hypothesized to be beneficial due to their ability to reduce elevated ER stress in vitro and in vivo, offering a potential therapeutic avenue.

This project establishes a precision-medicine oriented Rare Diabetes Clinic for Wolfram Syndrome patients. Researchers will prospectively follow a cohort of subjects with Wolfram Syndrome Type 1 in an interventional protocol using tirzepatide, a dual GIP/GLP-1 receptor agonist. This is a prospective Phase 2, non-randomized, single-group assignment intervention trial. The primary objective is to determine the efficacy of tirzepatide in increasing endogenous insulin production and correcting glycemic lability in these patients.