Tirzepatide Monotherapy in Patients With Wolfram Syndrome Type 1
Status:
Not yet recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
Summary
Wolfram syndrome (WFS:OMIM 222300) is a group of inherited disorders that usually appear in
childhood and cause diabetes, optic atrophy leading to loss of vision, deafness and often
diabetes insipidus. Wolfram syndrome affected no more than 0.2 in 10,000 people in the
European Union. There is no cure and no treatment that will arrest or delay the progress of
the disease.
The gene responsible for WS1 is WFS1, it encodes for wolframin, a transmembrane glycoprotein
involved in the regulation of the unfolded protein response. Recently, drug repurposing has
been hypothesized from others and us as being useful for WS1 therapy. More specifically,
GLP-1 receptor agonists were suggested as a promising class of anti- diabetic drugs having
the potential to delay or even reverse disease progression based on their ability to reduce
elevated ER stress in vitro and in vivo.
The objective of this project is to create a model of precision-medicine oriented Rare
Diabetes Clinic, which will be specifically dedicated to the treatment and follow-up of
complex patients with Wolfram Syndrome. A team of clinicians and researchers specialized in
diabetes and/or optic neuropathy and with experience in the subset of monogenic forms will
make available a cohort of subjects with Wolfram Syndrome prospectively followed in an
interventional protocol on the use of tirzepatide (a dual glucose-dependent insulinotropic
polypeptide and glucagon-like peptide-1 receptor agonist). It will be a prospective phase 2,
non-randomized, single group assignment, intervention trial to determine the efficacy of
tirzepatide (GIP/GLP-1 receptor agonist) in increasing endogenous insulin production and
correcting glycemic lability in patients with Wolfram syndrome type 1 (WS1).
The expected outcomes of this study are 1) to provide a therapeutic option for a devastating
orphan disease; 2) to confirm the efficacy of a repurposed drug able to reduce elevated
endoplasmic reticulum (ER) stress in a disease that represents a model of ER disease; 3) to
confirm the efficacy of the disease modeling based on iPSC to predict the response to
treatment; 4) to develop a disease-specific multidisciplinary follow-up.