View clinical trials related to Wolfram Syndrome.
Filter by: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.
Open label, phase II study non randomized single group assignment of 20 evaluable patients 13 years and older, over 37,5 kg body-weight, with sensorineural hearing loss of at least 20 dB at 8 kHz in high frequency average (HFA), and with documented genetic mutations in the WFS1 gene and with at least one other major documented clinical symptom pertaining to Wolfram syndrome (i.e. diabetes mellitus, diabetes insipidus, optic atrophy). Every patients will receive over three years a treatment by VPA (Depakine chrono).
The study has two aims: 1. To (1a) determine the frequency of monogenic diabetes misdiagnosed as type 1 diabetes (T1D) and (2) to define an algorithm for case selection. 2. To discover novel genes whose mutations cause monogenic diabetes misdiagnosed as T1D.
In this study, the investigators hypothesize that studying monogenic variants with strong effect associated with severe insulin deficiency of Wolfram syndrome will provide important insights into the more complex type 1 and type 2 diabetes mellitus. Aim 1. Establish and maintain a registry of patients with Wolfram syndrome. An Internet based registry will be employed to enroll participants with the clinical diagnosis of Wolfram syndrome (insulin dependent DM and bilateral OA). Clinical information regarding age of diagnosis and progression of the disease will be collated and analyzed to better define its natural history, along with potential metabolic phenotypes such as glucose intolerance of heterozygous parents and unaffected sibs. If not already completed, blood for WFS1 sequence analysis will be obtained on the participants (parents and sibs also for control purposes) and sent to a CLIA certified lab to define the mutation. This information will benefit patient families and referring physicians by providing a genetic diagnosis and where indicated. The Wolfram Syndrome Registry will foster international collaborations to more efficiently and systematically collect Wolfram syndrome patients and their clinical and experimental data.