Reciprocal rescue of Wolfram syndrome by two causative genes
EMBO Rep. 2025 Apr 3. doi: 10.1038/s44319-025-00436-2. Online ahead of print. ABSTRACT Wolfram syndrome (WS) is marked by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. The causative genes, WFS1 and CISD2, correspond to WS types 1 and 2, respectively. Here, we establish their mutual indispensability for inositol 1,4,5-triphosphate receptor (IP3R) activity, […]
Atypical Forms of Diabetes
2025 Mar 10. In: Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Muzumdar R, Purnell J, […]
Nuclear factor erythroid 2-related factor improves depression and cognitive dysfunction in rats with ischemic stroke by mediating wolfram syndrome 1
Brain Res. 2025 Mar 16:149572. doi: 10.1016/j.brainres.2025.149572. Online ahead of print. ABSTRACT OBJECTIVE: This research aims to investigate the molecular mechanism of nuclear factor erythroid 2-related factor (Nrf2) in improving post-stroke depression and cognitive impairment (PSDCI) by mediating wolfram syndrome 1 (Wfs1). METHODS: PSDCI rat model was established through middle cerebral artery occlusion (MCAO) and […]
Natural history of patients with autosomal dominant WFS1 pathogenic variants associated with sensorineural hearing loss and optic atrophy
medRxiv [Preprint]. 2025 Feb 25:2025.02.23.25322342. doi: 10.1101/2025.02.23.25322342. ABSTRACT OBJECTIVE: Autosomal dominant pathogenic variants in the WFS1 gene can cause a broad spectrum of WFS1-related disorders. These disorders present with a range of phenotypic manifestations, including isolated low-frequency sensorineural hearing loss, optic nerve atrophy accompanied by low- to mid-frequency sensorineural hearing loss, isolated diabetes mellitus, and […]
GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome
Diabetol Metab Syndr. 2025 Mar 6;17(1):82. doi: 10.1186/s13098-025-01651-6. ABSTRACT BACKGROUND AND AIM: Wolfram syndrome (WS) is a rare autosomal disorder caused by WFS1 gene mutations, currently lacking approved treatments. Preclinical and clinical reports suggest that diabetes medications, such as glucagon-like peptide-1 receptor agonist (GLP1-RA), slow WS-related diabetes and neurodegeneration, improving patient outcomes. Gamma-aminobutyric acid (GABA) […]
Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial
BMJ Open. 2025 Feb 26;15(2):e091495. doi: 10.1136/bmjopen-2024-091495. ABSTRACT INTRODUCTION: Wolfram syndrome (WFS1-Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration […]
beta cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome
Sci Transl Med. 2025 Feb 19;17(786):eadp2332. doi: 10.1126/scitranslmed.adp2332. Epub 2025 Feb 19. ABSTRACT Insulin-dependent diabetes in patients with Wolfram syndrome (WS; OMIM 222300) has been linked to endoplasmic reticulum (ER) stress caused by WFS1 gene mutations. However, the pathological process of ER stress-associated β cell failure remains to be fully elucidated. Our results indicate loss […]
Identification of a pathogenic founder variant in the WFS1 gene that causes Wolfram syndrome in the Druze population
Front Pediatr. 2025 Jan 29;13:1525846. doi: 10.3389/fped.2025.1525846. eCollection 2025. ABSTRACT CONTEXT: Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder caused by pathogenic variants in the WFS1 gene. It is characterized by central diabetes insipidus, juvenile-onset diabetes mellitus (DM), optic atrophy (OA), and deafness. The natural history of WS is variable, even within the same […]
The Role of Visual Electrophysiology in Systemic Hereditary Syndromes
Int J Mol Sci. 2025 Jan 23;26(3):957. doi: 10.3390/ijms26030957. ABSTRACT Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal electroretinography […]
Do wolframin, P-glycoprotein, and GRP78/BiP cooperate to alter the response of L1210 cells to endoplasmic reticulum stress or drug sensitivity?
Cancer Cell Int. 2025 Feb 7;25(1):35. doi: 10.1186/s12935-025-03661-w. ABSTRACT In previous research, we revealed that murine leukemia cells L1210 with induced expression of P-glycoprotein (P-gp, a membrane drug transporter, product of the Abcb1 gene) are better able to withstand endoplasmic reticulum (ER) stress (ERS) than their P-gp negative counterparts. This was associated with increased GRP78/BiP […]