Article
Ophthalmology
Juanjuan Zhang, Yanchun Ji, Jie Chen, Man Xu, Guoping Wang, Xiaorui Ci, Bing Lin, Jun Q. Mo, Xiangtian Zhou, Min-Xin Guan
Summary: Our study highlights the crucial role of the m.3460G>A mutation in the pathogenesis of LHON, characterized by mitochondrial dysfunction and alterations in apoptosis and mitophagy.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Hui-Chen Cheng, Sheng-Chu Chi, Chiao-Ying Liang, Jenn-Yah Yu, An-Guor Wang
Summary: Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease caused by mitochondria DNA (mtDNA) mutation, with incomplete penetrance and male prevalence. Whole exome sequencing (WES) revealed that many mitochondria-related nuclear genes are involved in the penetrance of LHON, highlighting the potential of WES in identifying candidate genes in molecular genetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mirko Baglivo, Alessia Nasca, Eleonora Lamantea, Stefano Vinci, Manuela Spagnolo, Silvia Marchet, Holger Prokisch, Alessia Catania, Costanza Lamperti, Daniele Ghezzi
Summary: Leber's hereditary optic neuropathy (LHON) is a disease that causes visual loss due to damage to the optical nerve. In this study, the respiratory parameters of LHON patients' fibroblasts were evaluated, revealing reduced respiration in untreated conditions and no significant improvement after idebenone supplementation. The responsiveness of cultured cells to idebenone treatment did not fully reflect in vivo data, indicating the need for further evaluation of cellular respiration as a potential biomarker for LHON prognosis and treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Xiaofen Jin, Juanjuan Zhang, Qiuzi Yi, Feilong Meng, Jialing Yu, Yanchun Ji, Jun Q. Mo, Yi Tong, Pingping Jiang, Min-Xin Guan
Summary: This study investigated the synergic interaction between LHON-associated ND1 and YARS2 mutations, revealing that the mutations lead to greater mitochondrial defects and increased autophagy. The ND1 mutation altered protein structure and function, while the YARS2 mutation affected protein stability. Cells harboring both mutations exhibited more severe deficiencies in mitochondrial function and showed higher levels of autophagy compared to cells with only one mutation.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Cell Biology
Jane W. Chan, William Sultan, Rustum Karanjia, Alfredo A. Sadun
Summary: In this study, the visual effects of pharmacologic intervention with 4-aminopyridine (4-AP) in chronic Leber's Hereditary Optic Neuropathy (LHON) patients were examined. The addition of 4-AP showed potential for visual recovery in some LHON patients, but was ineffective in others.
Article
Ophthalmology
Felix Tonagel, Helmut Wilhelm, Paul Richter, Carina Kelbsch
Summary: The study investigated two cohorts of LHON patients, with one receiving no medication and the other receiving a daily dose of 900 mg idebenone. The findings suggest that idebenone may improve vision in some LHON patients, with three out of seven patients in the treated cohort experiencing visual acuity recovery.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2021)
Article
Medicine, General & Internal
Berthold Pemp, Christoph Mitsch, Karl Kircher, Andreas Reitner
Summary: The study investigated the effects of idebenone treatment on visual function and retinal structure in LHON patients. Significant improvement in visual acuity was observed in acute and chronic patients after treatment, indicating a potential reactivation of signal transduction in surviving dysfunctional RGC.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cell & Tissue Engineering
Dongmei Ji, Xun Su, Chao Hu, Zhikang Zhang, Mengyao Wang, Weiwei Zou, Lingchao Shen, Yajing Liu, Chunmei Liang, Yinan Du, Dan Liang, Yunxia Cao
Summary: LHON is a mitochondrial disease that causes degeneration of retinal ganglion cells and optic atrophy in young adults. The majority of LHON cases are caused by three common mitochondrial DNA mutations, while another mutation affects the structure and function of the MT-ND1 gene. Researchers have generated a hiPSC line from an LHON patient with the MT-ND1 mutation.
STEM CELL RESEARCH
(2022)
Review
Medicine, General & Internal
Yi-Ping Yang, Shania Foustine, Yu-Jer Hsiao, En-Tung Tsai, Fu-Ting Tsai, Chia-Lin Wang, Yu-Ling Ko, Hsiao-Yun Tai, Yi-Ching Tsai, Chang-Hao Yang, Yun-Ju Fu, An-Guor Wang, Yueh Chien
Summary: In 2018, the prevalence of optic neuropathies was estimated to be 115 per 100,000 population. Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial disease first identified in 1871. It is associated with three mtDNA point mutations, namely G11778A, T14484, and G3460A, affecting NADH dehydrogenase subunits. The absence of NADH dehydrogenase due to the mutations leads to ATP production cessation, resulting in the generation of reactive oxygen species and apoptosis of retinal ganglion cells. Additionally, environmental factors such as smoking and alcohol consumption are considered risk factors for LHON. Gene therapy and human induced pluripotent stem cells (hiPSCs) have shown promise in LHON research.
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2023)
Article
Clinical Neurology
Martin Engvall, Aki Kawasaki, Valerio Carelli, Rolf Wibom, Helene Bruhn, Nicole Lesko, Florian A. Schober, Anna Wredenberg, Anna Wedell, Frank Traisk
Summary: Leber hereditary optic neuropathy (LHON) is a mitochondrial disease that causes severe bilateral visual loss, typically in young adults. This report discusses a mother and son with the typical LHON phenotype, but genetic investigations for the commonly found mutations were negative, revealing a new and previously unreported mutation in mitochondrial DNA. The new mutation, m.13345G>A, is located in the MT-ND5 gene, encoding a core subunit in complex I in the mitochondrial respiratory chain.
FRONTIERS IN NEUROLOGY
(2021)
Review
Genetics & Heredity
Qingyue Ma, Ying Sun, Ke Lei, Wenjuan Luo
Summary: This article summarizes the recent research progress on LHON, aiming to identify the genetic pathogenesis and clinical treatment points.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Clinical Neurology
Hong Ren, Yan Lin, Ying Li, Xiufang Zhang, Wei Wang, Xuebi Xu, Kunqian Ji, Yuying Zhao, Chuanzhu Yan
Summary: In this study, we report a unique case of Leber's hereditary optic neuropathy (LHON) with the rare m.4136A > G and m.4160 T > C variants. We elucidate the molecular pathomechanisms of the m.4160 T > C mutation and provide comprehensive data to further understand the pathogenicity of this variant.
NEUROLOGICAL SCIENCES
(2022)
Article
Ophthalmology
Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Jean Francois Girmens, Chiara La Morgia, Adam A. DeBusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, Francois Montestruc, Michel Roux, Magali Taiel, Jose-Alain Sahel, The Lhon Study Group
Summary: Lenadogene nolparvovec is a promising gene therapy for LHON patients with MT-ND4 mutation, showing sustained visual acuity improvement compared to natural history. Incorporation of data from the latest trial REFLECT indicates that bilateral injection may offer added benefits over unilateral injection.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Neurosciences
Shun Yao, Qingru Zhou, Mingzhu Yang, Ya Li, Xiuxiu Jin, Qingge Guo, Lin Yang, Fangyuan Qin, Bo Lei
Summary: This study found that multiple variations in mitochondrial genes are associated with the heterogeneity, especially phenotypic heterogeneity, in patients with Leber's hereditary optic neuropathy (LHON). Cells with more mtDNA variants showed higher levels of reactive oxygen species (ROS), lower mitochondrial membrane potential, and weaker respiratory function. Multiple mtDNA variants were also associated with different levels of cell viability and apoptosis.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Sylvie Gerber, Christophe Orssaud, Josseline Kaplan, Catrine Johansson, Jean-Michel Rozet
Summary: Pathological variants in the MCAT gene have been linked to optic nerve degeneration in childhood, and a wider phenotypic presentation of these mutations has been identified. An analysis of 51 families with negative molecular diagnostic tests revealed novel MCAT mutations in a female patient presenting with central visual loss.
Article
Cell Biology
Alberto Danese, Simone Patergnani, Alessandra Maresca, Camille Peron, Andrea Raimondi, Leonardo Caporali, Saverio Marchi, Chiara La Morgia, Valentina Del Dotto, Claudia Zanna, Angelo Iannielli, Alice Segnali, Ivano Di Meo, Andrea Cavaliere, Magdalena Lebiedzinska-Arciszewska, Mariusz R. Wieckowski, Andrea Martinuzzi, Milton N. Moraes-Filho, Solange R. Salomao, Adriana Berezovsky, Rubens Belfort, Christopher Buser, Fred N. Ross-Cisneros, Alfredo A. Sadun, Carlo Tacchetti, Vania Broccoli, Carlotta Giorgi, Valeria Tiranti, Valerio Carelli, Paolo Pinton
Summary: Patients with Leber's hereditary optic neuropathy (LHON) exhibit sustained abnormal autophagy and compartment-specific mitophagy activity, disrupting mitochondrial homeostasis and leading to defective bioenergetics and excessive reactive oxygen species production. Modulating autophagy and mitochondrial biogenesis can counteract this pathological mechanism.
Review
Pharmacology & Pharmacy
Alessia Di Donfrancesco, Giulia Massaro, Ivano Di Meo, Valeria Tiranti, Emanuela Bottani, Dario Brunetti
Summary: This article provides a comprehensive overview of the application of gene therapy in mitochondrial diseases (MDs), addressing the main challenges, feasible solutions, and future prospects.
Review
Biochemistry & Molecular Biology
Marco D'Amato, Francesca Morra, Ivano Di Meo, Valeria Tiranti
Summary: Mitochondrial diseases are genetic conditions caused by mutations in nuclear or mitochondrial DNA. Existing therapies are insufficient for treating the wide range of mtDNA mutations. Mitochondrial transplantation offers a potential solution by transferring healthy mitochondria to dysfunctional cells or tissues. This review explores the mechanisms and methods of intercellular mitochondrial transfer and discusses its potential therapeutic applications. Mitochondrial transplantation could induce a shift in heteroplasmy and potentially attenuate or prevent pathological phenotypes. However, further research is needed before its widespread use in mitochondrial medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Leonardo Caporali, Claudio Fiorini, Flavia Palombo, Martina Romagnoli, Flavia Baccari, Corrado Zenesini, Paola Visconti, Annio Posar, Maria Cristina Scaduto, Danara Ormanbekova, Agatino Battaglia, Raffaella Tancredi, Cinzia Cameli, Marta Viggiano, Anna Olivieri, Antonio Torroni, Elena Maestrini, Magali Jane Rochat, Elena Bacchelli, Valerio Carelli, Alessandra Maresca
Summary: Research has found that mtDNA plays a role in the development and expression of ASD, particularly with a protective effect from paternal mtDNA in the Italian population. Additionally, ASD patients have lower mtDNA content. Further confirmation is needed in larger independent cohorts.
FRONTIERS IN GENETICS
(2022)
Article
Pharmacology & Pharmacy
Paolo Santambrogio, Anna Cozzi, Ivano Di Meo, Chiara Cavestro, Cristina Vergara, Laura Rodriguez-Pascau, Marc Martinell, Pilar Pizcueta, Valeria Tiranti, Sonia Levi
Summary: This study tested the effectiveness of the brain-penetrant peroxisome proliferator-activated receptor gamma agonist leriglitazone in ameliorating mitochondrial defects in a cellular model of Pantothenate kinase-2 associated Neurodegeneration (PKAN). The results showed that leriglitazone improved the viability and respiratory activity of PKAN cells, while reducing iron accumulation, suggesting it could be a beneficial therapeutic approach for PKAN treatment.
Review
Biochemistry & Molecular Biology
Isabella Tolle, Valeria Tiranti, Alessandro Prigione
Summary: Mitochondrial DNA (mtDNA) diseases are multi-systemic disorders caused by mutations affecting mtDNA copies. Current obstacles in engineering mtDNA have hindered the study of mtDNA defects. However, recent advances in base editing of mtDNA and generation of organoids from patient-derived iPSCs provide valuable tools for understanding mtDNA diseases and identifying potential treatment strategies.
Review
Biochemistry & Molecular Biology
Chiara Cavestro, Daria Diodato, Valeria Tiranti, Ivano Di Meo
Summary: Coenzyme A (CoA) is an essential cofactor that plays a vital role in numerous enzymatic reactions and cellular processes. Four rare human inborn errors of CoA biosynthesis have been described, all stemming from variants in genes encoding enzymes involved in the same metabolic process. This review provides an overview of CoA metabolism and functions, and summarizes the current knowledge on disorders associated with its biosynthesis, including proposed pathomechanisms and potential therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Chiara Vasco, Ambra Rizzo, Chiara Cordiglieri, Elena Corsini, Emanuela Maderna, Emilio Ciusani, Andrea Salmaggi
Summary: Metastasis refers to the spread of a tumor from its original site to other parts of the body. This study focused on brain metastasis and used an in vitro model to investigate the ability of breast and lung tumor cells to cross the blood-brain barrier, as well as the expression of adhesion molecules. The study also found that vesicles released by tumor cells can induce cell death in endothelial cells.
Article
Psychology, Developmental
Silvia Annunziata, Sara Bulgheroni, Stefano D'Arrigo, Silvia Esposito, Matilde Taddei, Veronica Saletti, Enrico Alfei, Francesca Luisa Sciacca, Ambra Rizzo, Chiara Pantaleoni, Daria Riva
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental condition with a strong genetic basis. This study found that complex ASD patients have a higher frequency of pathogenic genetic mutations, highlighting the importance of detailed phenotypic characterization in ASD diagnosis and research.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Flavia Palombo, Camille Peron, Leonardo Caporali, Angelo Iannielli, Alessandra Maresca, Ivano Di Meo, Claudio Fiorini, Alice Segnali, Tiina Manninen, Francesca L. Sciacca, Ambra Rizzo, Sonia Levi, Anu Suomalainen, Alessandro Prigione, Vania Broccoli, Valerio Carelli, Valeria Tiranti
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Leonardo Caporali, Claudio Fiorini, Flavia Palombo, Flavia Baccari, Martina Romagnoli, Paola Visconti, Annio Posar, Maria Cristina Scaduto, Elena Maestrini, Cinzia Cameli, Marta Viggiano, Anna Olivieri, Antonio Torroni, Elena Bacchelli, Magali Rochat, Valerio Carelli, Alessandra Maresca
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
