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Beyond MT-ND4/MT-ND1, nuclear genes such as PRICKLE3, YARS2, and DNAJC30 influence disease mechanisms differently. Clinical and emerging therapies include idebenone, mesenchymal stem cell mitochondrial transfer, and gene therapy targeting wild-type ND4 using AAV 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LHON.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic approaches are discussed for LHON?",{"text":72,"@type":64},"The article highlights idebenone (approved and studied in clinical trials), mesenchymal stem cell-based mitochondrial transfer, and gene therapy using AAV vectors targeting wild-type ND4 to address specific gene mutations.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},436240,1790794962,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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\nLeber’s hereditary optic neuropathy: Update on the novel genes and therapeutic options  \nJui-Lin Hua, Chih-Chien Hsub,c, Yu-Jer Hsiaoc,d, Yi-Ying Lind, Wei-Yi Laid, Yu-Hao Liud, Chia-Lin Wangd, Yu-Ling Kod, Ming-Long Tsaid, Huan-Chin Tsengc,d, Yueh Chienc,d,* , Yi-Ping Yangc,d,*  \naInstitute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC; bDepartment of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; cSchool of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC; dDepartment of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC  \nAbstract  \nA maternal inheritance disorder called Leber’s hereditary optic neuropathy (LHON) is the most common primary mitochondrial deoxyribonucleic acid (DNA) disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective adenosine triphosphate (ATP) production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3 , YARS2 , and DNAJC30 , which come from nDNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11 .23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria. DNAJC30 mutations result in autosomal recessive LHON (arLHON) . Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the adeno-associated viruses (AAV) vector has shown promise in clinical trials as a potential treatment for LHON.  \nKeywords: Female; Male; Mitochondrial; Retinal ganglion cells; Tyrosyl-tRNA synthetase  \n1. INTRODUCTION  \nLeber’s hereditary optic neuropathy (LHON) is a rare ophthalmic disease with a prevalence between 1:30 000 to 1:50 000 in Europe. It is caused by point mutations in mitochondrial deoxyribonucleic acid (DNA), with the most common mutations being MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 . MT-ND4 is the predominant mutation worldwide, accounting for 70% of the cases in Europe and 90% in Asia. LHON patients experience severe bilateral visual loss and degeneration of retinal ganglion cells, typically starting in their teenage years or adulthood. LHON is characterized by painless optic neuropathy and optic atrophy that gradually reduces visual acuity permanently. The affected eye demonstrates an edematous appearance of the nerve fiber layer. Fundus examination can reveal pupillary deficiency that results in decreased visual acuity and loss of color vision. Diagnosis can also be made through blood testing for mitochondrial DNA, specifically the genes ND1, ND4, and ND6 which  \n* Address correspondence. Dr. Yueh Chien and Dr. Yi-Ping Yang, Department of Medical Research, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, 112 Taipei, Taiwan, [ROC. E-mail address: g39005005@gmail.com](ROC. E-mail address: g39005005@gmail.com) (Y. Chien); [molly0103@gmail.com](molly0103@gmail.com) (Y.-P. Yang).  \nConflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.  \nJournal of Chinese Medical Association. (2024) 87: 12-16.  \nReceived May 29, 2023; accepted July 9, 2023. doi: 10. 1097/JCMA.0000000000001031  \nCopyright © 2023, the Chinese Medical Association. This is an ope","cbCairwLjn0DpvI1","https://ap.wps.com/l/cbCairwLjn0DpvI1","pdf",773697,"English","# Abstract\n# 1. Introduction\n# 2. Novel nuclear gene mutation in LHON","[{\"question\":\"What causes Leber’s hereditary optic neuropathy at the cellular level?\",\"answer\":\"LHON is driven primarily by dysfunction in mitochondrial complex I, leading to ineffective ATP production and increased reactive oxygen species, which promote apoptosis of retinal ganglion cells.\"},{\"question\":\"Why do more male patients than female patients develop LHON in many studies?\",\"answer\":\"The male predominance, which differs from typical mitochondrial inheritance patterns, suggests that nuclear DNA may modulate degeneration of retinal ganglion cells in LHON.\"},{\"question\":\"What therapeutic approaches are discussed for LHON?\",\"answer\":\"The article highlights idebenone (approved and studied in clinical trials), mesenchymal stem cell-based mitochondrial transfer, and gene therapy using AAV vectors targeting wild-type ND4 to address specific gene mutations.\"}]","Leber’s hereditary optic neuropathy: Update on the novel genes and therapeutic options | PDF",1790677301,13]