Fumihiko Urano

Hyperexcitable but seizure-free: hippocampal network dysfunction in a Wolfram syndrome model

This study investigates hippocampal network dysfunction in a Wolfram syndrome mouse model, finding hyperexcitable neurons without seizures or increased network bursting.

MANF Clears Mutant Uromodulin in Human Kidney Organoids of Autosomal Dominant Tubulointerstitial Kidney Disease

This study shows MANF reduces mutant uromodulin in kidney organoids by enhancing autophagy through IP3R1 repression, suggesting potential for treating ADTKD and similar protein misfolding diseases.

Genotype-Based Severity Scoring System in Wolfram Syndrome: Correlation with Onset of Cardinal Symptoms and WFS1 Gene Variant Types

Higher WFS1 genotype scores (variant frame, transmembrane location) tracked earlier diabetes mellitus and optic atrophy onset in 324 Wolfram patients, not hearing loss or diabetes insipidus.

Consensus Recommendations for the Clinical Management of Wolfram syndrome Using a Delphi Method

This paper develops international clinical guidelines for Wolfram syndrome using a Delphi method, resulting in 35 consensus statements with ≥80% agreement across multiple domains.

Synaptic Alterations Are Preceding the Axonal Loss in Optic Atrophy of Wolfram Syndrome Mouse Model

The paper investigates synaptic and dendritic abnormalities in the retina of Wfs1 knockout mice, finding that synaptic alterations precede axonal loss in a Wolfram syndrome model.

Natural history of patients with autosomal dominant WFS1 pathogenic variants associated with sensorineural hearing loss and optic atrophy

This study analyzes clinical data from 11 patients with autosomal dominant WFS1 variants to describe the natural history of optic atrophy and sensorineural hearing loss, identifying a novel variant and providing insights into disease progression.

Dual Role of Neuroplastin in Pancreatic Beta Cells: Regulating Insulin Secretion and Promoting Islet Inflammation

This study identifies Neuroplastin as a binding partner of MANF in pancreatic beta cells, showing it regulates insulin secretion, proliferation, and inflammation, with MANF counteracting these effects.

Genotype and Clinical Characteristics of Patients with Wolfram Syndrome and WFS1-related Disorders

This study investigates the genotype-phenotype relationship in Wolfram syndrome, finding that specific WFS1 gene variants correlate with earlier onset and more severe disease manifestations.

Anti-inflammatory effects of WFS1 in pancreatic beta-cells

This study shows that WFS1 deficiency in pancreatic beta-cells increases inflammation, leading to ER stress and cell death, and identifies potential therapeutic targets for Wolfram syndrome.

Genotype-phenotype correlation analysis and therapeutic development using a patient stem cell-derived disease model of Wolfram syndrome

This study uses a patient-derived stem cell model to show that a specific WFS1 variant causes mild Wolfram syndrome, which can be treated with chemical chaperones.

Alterations in neuronal physiology, development, and function associated with a common duplication of chromosome 15 involving CHRNA7

This study uses iPSC models to show that a 15q13.3 duplication causes distinct neurodevelopmental and functional anomalies in an affected individual but not their unaffected mother, while both share increased cholinergic activity.

A Phase 1b/2a Clinical Trial of Dantrolene Sodium in Patients with Wolfram Syndrome

This paper reports a phase 1b/2a clinical trial of dantrolene sodium in Wolfram syndrome patients, showing it is well tolerated and showing some potential efficacy in beta-cell function and visual acuity.