Article
Pediatrics
Giulio Frontino, Tara Raouf, Daniele Canarutto, Eva Tirelli, Raffaella Di Tonno, Andrea Rigamonti, Maria Lucia Cascavilla, Cristina Baldoli, Roberta Scotti, Letizia Leocani, Su-Chun Huang, Franco Meschi, Graziano Barera, Vania Broccoli, Greta Rossi, Silvia Torchio, Raniero Chimienti, Riccardo Bonfanti, Lorenzo Piemonti
Summary: The study investigated the off-label treatment of liraglutide in pediatric patients with Wolfram Syndrome type 1, showing good safety and tolerability, as well as potential benefits in maintaining C-peptide secretion and stabilizing neuro-ophthalmological disease parameters.
FRONTIERS IN PEDIATRICS
(2021)
Article
Genetics & Heredity
Laura Alias, Miguel Lopez de Heredia, Sabina Luna, Nuria Cliville, Lidia Gonzalez-Quereda, Pia Gallano, Julia de Juan, Albert Pujol, Santiago Diez, Susana Boronat, Cesar Orus, Adriana Lasa, Maria del Prado Venegas
Summary: This study utilized genetic research to identify a pathogenic gene variant related to Wolfram-like syndrome in a young girl with congenital deafness. The early detection of the variant allowed for appropriate management and highlights the importance of next-generation sequencing in the diagnosis of hereditary deafness.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Evan M. Lee, Megha Verma, Nila Palaniappan, Emiko M. Pope, Sammie Lee, Lindsey Blacher, Pooja Neerumalla, William An, Toko Campbell, Cris Brown, Stacy Hurst, Bess Marshall, Tamara Hershey, Virginia Nunes, Miguel Lopez de Heredia, Fumihiko Urano
Summary: This study examines the relationship between genotype and phenotype presentations of Wolfram syndrome. The results indicate that the number and type of mutations in the WFS1 gene are associated with the severity and prognosis of the syndrome. Specifically, non-sense and frameshift variants result in more severe phenotypic presentations, while transmembrane in-frame variants affect the age of onset of diabetes mellitus and optic atrophy.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Marite Punapart, Kadri Seppa, Toomas Jagomae, Mailis Liiv, Riin Reimets, Silvia Kirillov, Allen Kaasik, Lieve Moons, Lies De Groef, Anton Terasmaa, Eero Vasar, Mario Plaas
Summary: Wolfram syndrome (WS) is a rare monogenic neurodegenerative disorder caused by mutations in the gene encoding WFS1 with no current treatment available. Research on a rat model of WS revealed early deviations in the renin-angiotensin-aldosterone system (RAAS) and bradykinin pathway (KKS), as well as the modulatory effect of glucagon-like peptide-1 receptor agonist liraglutide and anti-epileptic drug valproate. These treatments were shown to elevate serum aldosterone and decrease bradykinin levels in WS rats, indicating their potential to modulate these systems.
Article
Neurosciences
Sarah A. Eisenstein, Raveena S. Boodram, Courtney L. Sutphen, Heather M. Lugar, Brian A. Gordon, Bess A. Marshall, Fumihiko Urano, Anne M. Fagan, Tamara Hershey
Summary: Wolfram syndrome is a rare disease caused by pathogenic variants in the WFS1 gene, and currently there is no easily accessible biomarker for tracking the progression of neurodegeneration. This study suggests that plasma NfL levels can be a powerful tool to assess the underlying neurodegenerative processes in individuals with Wolfram syndrome, providing a non-invasive method for disease monitoring.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell & Tissue Engineering
Malgorzata Zatyka, Tatiana R. Rosenstock, Congxin Sun, Adina M. Palhegyi, Georgina W. Hughes, Samuel Lara-Reyna, Dewi Astuti, Alessandro di Maio, Axel Sciauvaud, Miriam E. Korsgen, Vesna Stanulovic, Gamze Kocak, Malgorzata Rak, Sandra Pourtoy-Brasselet, Katherine Winter, Thiago Varga, Margot Jarrige, Helene Polveche, Joao Correia, Eva-Maria Frickel, Maarten Hoogenkamp, Douglas G. Ward, Laetitia Aubry, Timothy Barrett, Sovan Sarkar
Summary: Wolfram syndrome (WS) is a rare early-onset neurodegenerative disease that is associated with mitochondrial abnormalities. The loss of interaction between WFS1 and VDAC1 in WS cells can compromise mitochondrial function, but restoring WFS1 levels can improve mitochondrial function and network. Therefore, targeting WFS1 or modulating mitochondrial function may provide a therapeutic intervention for WS and similar diseases.
Article
Ophthalmology
Anna Majander, Neringa Jurkute, Florence Burte, Kristain Brock, Catarina Joao, Houbin Huang, Magella m. Neveu, Choi mun Chan, Holly j. Duncan, Simon Kelly, Emma Burkitt-Wright, Fadil Khoyratty, Yoon tse Lai, Mala Subash, Patrick f. Chinnery, Maria Bitner-Glindzicz, Gavin Arno, Andrew r. Webster, Anthony t. Moore, Michel Michaelides, Andrew Stockman, Anthony g. Robson, Patrick Yu-Wai-Man
Summary: This study evaluates the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON). The results show that WFS1 variants cause severe loss of retinal ganglion cells, but with some variability and correlation with the mode of inheritance.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Cell Biology
Lucie Crouzier, Alberto Danese, Yuko Yasui, Elodie M. Richard, Jean-Charles Lievens, Simone Patergnani, Simon Couly, Camille Diez, Morgane Denus, Nicolas Cubedo, Mireille Rossel, Marc Thiry, Tsung-Ping Su, Paolo Pinton, Tangui Maurice, Benjamin Delprat
Summary: This study found that activating the S1R receptor can counteract the functional abnormalities of MAMs in Wolfram syndrome. The S1R agonist restores calcium ion transfer and mitochondria! respiration, corrects increased autophagy and mitophagy, and alleviates behavioral symptoms.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Kun Hu, Malgorzata Zatyka, Dewi Astuti, Nicola Beer, Renuka P. Dias, Archana Kulkarni, John Ainsworth, Benjamin Wright, Anna Majander, Patrick Yu-Wai-Man, Denise Williams, Timothy Barrett
Summary: This study found that patients with WFS who have partial WFS1 protein expression present with milder visual impairment, suggesting a protective effect of partial WFS1 protein expression on the severity and progression of vision impairment. Therapies to increase residual WFS1 protein expression may be beneficial for these patients.
JOURNAL OF MEDICAL GENETICS
(2022)
Review
Ophthalmology
Cansu de Muijnck, Jacoline B. ten Brink, Arthur A. Bergen, Camiel J. F. Boon, Maria M. van Genderen
Summary: Wolfram-like syndrome (WFLS) is an autosomal dominant disorder that shares similar phenotypic features with autosomal recessive Wolfram syndrome (WS), including optic atrophy, hearing impairment, and diabetes mellitus. This review summarizes current literature, identifies the clinical characteristics, and explores the potential genotype-phenotype correlations. The findings suggest that WFLS has a relatively milder phenotype compared to WS, with optic atrophy and hearing impairment being the most common manifestations. Diabetes mellitus and cataract can also occur in a significant proportion of patients. The specific mutations in the WFS1 gene are associated with the age at onset and severity of the clinical manifestations. Rating: 8 out of 10.
SURVEY OF OPHTHALMOLOGY
(2023)
Article
Pediatrics
Valentina Di Iorio, Enza Mozzillo, Francesco Maria Rosanio, Francesca Di Candia, Rita Genesio, Francesco Testa, Claudio Iovino, Adriana Franzese, Francesca Simonelli
Summary: Wolfram syndrome (WFS) is a rare neurodegenerative disease characterized by diabetes mellitus and optic atrophy. WFS can be classified into two types based on genetic mutations, with different accompanying complications. Patients with WFS2 and CISD2 intragenic deletion may exhibit slowly progressive optic neuropathy instead of typical optic atrophy.
FRONTIERS IN PEDIATRICS
(2021)
Article
Multidisciplinary Sciences
Kadri Seppa, Toomas Jagomae, Kaia Grete Kukker, Riin Reimets, Marko Pastak, Eero Vasar, Anton Terasmaa, Mario Plaas
Summary: Liraglutide, 7,8-DHF, and their combination treatment all showed protective effects in the WS rat model, including preventing lateral ventricle enlargement, improving learning, reducing inflammation, delaying optic nerve atrophy progression, and enhancing visual acuity.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Lucie Crouzier, Elodie M. Richard, Camille Diez, Morgane Denus, Amandine Peyrel, Hala Alzaeem, Nicolas Cubedo, Thomas Delaunay, Tangui Maurice, Benjamin Delprat
Summary: Wolfram syndrome (WS) is a rare neurodegenerative disease with no current treatment options. The mutated gene WFS1 encodes a protein called Wolframin, which plays a role in regulating calcium transfer and mitochondrial activity. Using a zebrafish model of WS, researchers found that overexpression of the NCS1 protein can restore mitochondrial dysfunction and excessive locomotion, suggesting a potential therapeutic strategy for WS.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Ophthalmology
Piero Barboni, Giulia Amore, Maria Lucia Cascavilla, Marco Battista, Giulio Frontino, Martina Romagnoli, Leonardo Caporali, Cristina Baldoli, Laura Ludovica Gramegna, Elisa Sessagesimi, Riccardo Bonfanti, Andrea Romagnoli, Roberta Scotti, Maria Brambati, Michele Carbonelli, Vincenzo Starace, Claudio Fiorini, Roberta Panebianco, Vincenzo Parisi, Caterina Tonon, Francesco Bandello, Valerio Carelli, Chiara La Morgia
Summary: This study describes the clinical phenotype of patients with Wolfram syndrome (WS), highlighting the severe optic atrophy and faster deterioration of visual function and structural parameters observed in WS patients compared to patients with OPA1-related dominant optic atrophy (DOA). The study also reveals thinning of the anterior optic pathway, particularly the prechiasmatic optic nerves and optic tracts, in WS patients based on MRI measurements. Furthermore, the OCT findings suggest that retinal ganglion cell axonal degeneration (RNFL) precedes cellular body atrophy (GCL) by about a decade in WS patients.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Genetics & Heredity
Hailey Mair, Nicholas Fowler, Maria E. Papatzanaki, Padmaja Sudhakar, Ramiro S. Maldonado
Summary: This study presents the deep phenotyping analysis of a mother and son carrying a novel WFS1 gene variant. Both the patient and the mother showed sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. The WFS1 variant was identified through a broader inherited retinal dystrophy panel.
OPHTHALMIC GENETICS
(2022)
Letter
Ophthalmology
Peter van Wijngaarden, Xavier Hadoux, Eirini Christinaki, Lies De Groef, Ingeborg Stalmans
CLINICAL AND EXPERIMENTAL OPTOMETRY
(2023)
Article
Cell Biology
An Beckers, Luca Masin, Annelies Van Dyck, Steven Bergmans, Sophie Vanhunsel, Anyi Zhang, Tine Verreet, Fabienne E. Poulain, Karl Farrow, Lieve Moons
Summary: This study reveals the phenomenon of mitochondrial shift between dendrites and axons during optic nerve injury-induced regeneration in zebrafish, and suggests that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.
NEURAL REGENERATION RESEARCH
(2023)
Article
Geriatrics & Gerontology
Steven Bergmans, Pieter-Jan Serneels, Luca Masin, Lieve Moons
Summary: The fast-aging killifish has become a popular model organism in studying age-related processes and neurodegeneration. However, studying neurodegeneration in the killifish's ever-growing brain and retina is complicated. Different tissue sampling methods revealed age-dependent reduction in cell density in the retina, but whole-mount retinas did not detect any neuron loss. The analysis also showed that retinal growth at old age is primarily driven by tissue stretching, leading to a decrease in neuronal density.
Article
Clinical Neurology
Marine Tessier, Marta Saez Garcia, Emmanuelle Goubert, Edith Blasco, Amandine Consumi, Benoit Dehapiot, Li Tian, Florence Molinari, Jerome Laurin, Francois Guillemot, Christian A. Huebner, Christophe Pellegrino, Claudio Rivera
Summary: The study reveals a novel mechanism of action for the Na-K-Cl cotransporter (NKCC1) inhibitor bumetanide in neurological disorders. It shows that bumetanide accelerates microglial activation dynamics, resulting in an increase in parvalbumin interneuron survival through increased microglial BDNF expression and contact with interneurons.
Letter
Clinical Neurology
Nayana Gaur, Robert Steinbach, Mario Plaas, Otto W. Witte, Monika S. Brill, Julian Grosskreutz
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Mahvish Faisal, Jana Aid, Bekzod Nodirov, Benjamin Lee, Miriam A. A. Hickey
Summary: This study estimated the sample sizes and effect sizes for behavioral and neuropathological outcome measures in TG 5xFAD mice. The results showed that the group size needed to detect normalization of body weight and open-field hyperactivity was small. For cognitive tests and neuropathological outcomes, the required sample size varied depending on the specific measure.
Review
Anatomy & Morphology
Cristiano Lucci, Lies De Groef
Summary: In the last decade, extracellular vesicles (EVs) have gained attention for their potential to facilitate cell-to-cell communication, act as drug delivery vehicles, and serve as biomarkers. However, the role of EVs in glaucoma has not been thoroughly investigated. This article provides an overview of EV subtypes, their biogenesis, and content. Furthermore, it explores how EVs released by different cell types can contribute to glaucoma, and discusses the potential of EVs as biomarkers for diagnosis and disease monitoring.
FRONTIERS IN NEUROANATOMY
(2023)
Article
Neurosciences
Annelies Van Dyck, Luca Masin, Steven Bergmans, Giel Schevenels, An Beckers, Benoit Vanhollebeke, Lieve Moons
Summary: Unlike mammals, adult zebrafish can fully regenerate axons and recover from neuronal damage in the central nervous system. By studying optic nerve injury-induced axonal regrowth in zebrafish, researchers have observed dendritic remodeling and changes in mitochondrial dynamics, which contribute to effective axonal and dendritic repair. A novel microfluidic model has been developed to investigate these interactions and explore how redirecting energy resources supports successful regeneration.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Marite Punapart, Riin Reimets, Kadri Seppa, Silvia Kirillov, Nayana Gaur, Kattri-Liis Eskla, Toomas Jagomae, Eero Vasar, Mario Plaas
Summary: Biallelic mutations in the WFS1 gene cause Wolfram syndrome (WS), a rare neurodegenerative disorder without a cure. This study finds that the expression of key components of the renin-angiotensin-aldosterone system (RAAS) is dysregulated in neural tissue from aged WS rats and is unaffected by pharmacological treatments. The downregulation of angiotensin II receptors and bradykinin receptor B1 is observed in the hippocampus of WS animals experiencing chronic experimental stress, suggesting that WFS1 deficiency disrupts RAAS functioning and exacerbates neurodegeneration in WS.
Article
Neurosciences
Lien Andries, Daliya Kancheva, Luca Masin, Isabelle Scheyltjens, Hannah Van Hove, Karen De Vlaminck, Steven Bergmans, Marie Claes, Lies De Groef, Lieve Moons, Kiavash Movahedi
Summary: The multifaceted nature of neuroinflammation can both aggravate and promote neuronal health. In this study, we investigated the inflammatory response to optic nerve injury and found that inflammatory stimulation can recruit macrophages and promote axonal regrowth. This work reveals the potential of using inflammation to drive CNS regeneration and highlights the importance of macrophages in neuronal repair.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Cell Biology
Junhua Xie, Lien Cools, Griet Van Imschoot, Elien Van Wonterghem, Marie J. Pauwels, Ine Vlaeminck, Chloe De Witte, Samir EL Andaloussi, Keimpe Wierda, Lies De Groef, Freddy Haesebrouck, Lien Van Hoecke, Roosmarijn E. Vandenbroucke
Summary: The gut microbiota and its interaction with pathogens like Helicobacter pylori play a significant role in the development of Alzheimer's disease, with outer membrane vesicles acting as important carriers of virulence factors.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Review
Cell Biology
Steven Bergmans, Laura Raes, Lieve Moons, Lies De Groef
Summary: Thanks to medical and technological improvements, the world population is aging, leading to an increase in age-related central nervous system neuropathies. Current research using animal models lacks construct validity, as it does not fully replicate the complex cellular context of these diseases. The African turquoise killifish is emerging as a promising model to study age-related neurodegenerative disorders, as it combines the complex disease context with an aging environment.
AGEING RESEARCH REVIEWS
(2023)
Article
Physics, Applied
Sirli Raud, Juri Raud, Lauri Aarik, Indrek Jogi, Markus Kivimae, Carl-Thomas Piller, Mario Plaas, Toomas Plank, Rasmus Talviste, Tambet Teesalu, Eero Vasar
Summary: The present study investigated the production of reactive chlorine species (RCS) by Ar/O-2 and He/O-2 radiofrequency plasma jets in saline solution, and the sensitivity of the liver cancer cell line HepG2 to RCS and H2O2. Both plasma jets were able to produce RCS; however, the He/O-2 jet was more efficient for RCS production. The lower RCS yield in the case of the Ar/O-2 plasma jet was mainly due to the higher RCS quenching. Viability tests showed that HepG2 cells were more sensitive to H2O2 than RCS.
PLASMA PROCESSES AND POLYMERS
(2023)