Review
Biochemistry & Molecular Biology
Mani S. Mahadevan, Ramesh S. Yadava, Mahua Mandal
Summary: DM1 is a multi-systemic disorder affecting various organs, with the heart being one of the most severely impacted. Cardiac conduction defects and arrhythmias are common in adults with DM1, leading to potential sudden death. Understanding of cardiac pathology in DM1 is still limited, with cardiac magnetic resonance imaging (CMR) emerging as a valuable biomarker.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Lubov Timchenko
Summary: Myotonic Dystrophies type 1 (DM1) and type 2 (DM2) are complex multisystem diseases without disease-based therapies. DM1 is associated with the toxicity of RNA CUG repeats, leading to disturbances in RNA metabolism. The pathogenesis of DM2 is not fully understood. Progress has been made in translating mechanistic knowledge in DM1 and DM2 to clinical trials, focusing on the development of disease-specific therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mikel Garcia-Puga, Ander Saenz-Antonanzas, Ander Matheu, Adolfo Lopez de Munain
Summary: Myotonic dystrophy type 1 (DM1) is a genetic multisystemic disorder resembling accelerated aging, for which there is currently no cure. However, recent studies have shown that metformin, an antidiabetic drug, may provide a novel therapy to combat DM1 and is linked with aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Li Yang, Xiuying Chen, Rui Wu
Summary: Afterdischarges may be present in DM1 patients during electrodiagnostic testing. A study comparing DM1 and non-DM1 myotonia patients found afterdischarges to be prevalent in DM1 patients, but absent in non-DM1 myotonia patients. Therefore, afterdischarges may serve as a clinical indicator for DM1 diagnosis.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Matteo Garibaldi, Antonio Lauletta, Elisabetta Bucci, Laura Fionda, Fiammetta Vanoli, Luca Leonardi, Girolamo Alfieri, Laura Tufano, Stefania Morino, Gioia Merlonghi, Paolo Anibaldi, Marco Salvetti, Marco Testa, Giovanni Antonini
Summary: The risk of cardiac conduction abnormalities in DM1 is significantly higher in males than females, while there is no significant gender difference in overall CCRA, cardiac rhythm abnormalities, and SCD prevalence.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Thiery De Serres-Berard, Siham Ait Benichou, Dominic Jauvin, Mohamed Boutjdir, Jack Puymirat, Mohamed Chahine
Summary: DM1 is a dominant genetic disease that can be treated by altering the chemical design of antisense oligonucleotides. Various strategies involving chemical modifications and conjugation with specific functional molecules have been shown to improve the potency in muscle and cardiac tissues. In addition, intrathecal administration can be used to treat central nervous system defects in DM1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Xiaopeng Shen, Zhongxian Liu, Chunguang Wang, Feng Xu, Jingyi Zhang, Meng Li, Yang Lei, Ao Wang, Chao Bi, Guoping Zhu
Summary: The research discovered that Postn gene was significantly upregulated in DM1 myogenesis, and knocking down Postn could successfully rescue myogenesis defects, suggesting that Postn could be a potential therapeutic target for treating myogenesis defects in DM1.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Ye Zhang, Rong Ren, Linghui Yang, Hui Jin, Yuru Nie, Haipeng Zhang, Yuan Shi, Larry D. Sanford, Michael V. Vitiello, Xiangdong Tang
Summary: This study explores the differences in polysomnographic and multiple sleep latency test (MSLT) between myotonic dystrophy type 1/type 2 (DM1/DM2) patients and controls. The results reveal significant abnormalities in the polysomnographic sleep of DM1 patients, while differences in polysomnographic sleep change between DM2 patients and controls could not be established due to limited studies.
Article
Cardiac & Cardiovascular Systems
Isis B. T. Joosten, Romy van Lohuizen, Dennis W. den Uijl, Reinder Evertz, Bianca T. A. de Greef, Baziel G. M. van Engelen, Catharina G. Faber, Kevin Vernooy
Summary: This study aimed to determine ECG criteria predicting abnormal infrahissian conduction in patients with DM1, finding that a combination of prolonged PR interval and widened QRS complex accurately predicts delayed conduction. These criteria could be used as a screening tool to identify the need for referral to a specialized team with EPS capacity.
Editorial Material
Behavioral Sciences
Sara Leddy, Mara Cercignani, Laura Serra, Marco Bozzali
Summary: Research in social cognitive neuroscience aims to understand the neurobiology underlying social behaviors, and individuals with myotonic dystrophy may have difficulties in social cognitive function, highlighting the need for further research and management.
Article
Clinical Neurology
David Varga, Brigitta Perecz, Krisztina Fulop, Andrea Sipos, Jozsef Vlagyimir Janszky, Nandor Hajdu, Endre Pal
Summary: This study investigated the role of urinary titin as a biomarker for muscle injury in DM1. It found that the titin/creatinine ratio was significantly higher in DM1 patients compared to healthy controls, and it was related to the severity of muscle impairment. Urinary titin may be a potential biomarker for DM1 and further long-term follow-up is needed to explore its role in disease activity and progression.
Article
Biology
Lauren L. Ozimski, Maria Sabater-Arcis, Ariadna Bargiela, Ruben Artero
Summary: Myotonic dystrophy type 1 (DM1) is the most prevalent form of muscular dystrophy in adults with no current treatment options. The disease is mainly characterised by muscle pathology and affects patients worldwide. Research into various pathways affected in DM1 may provide new therapeutic targets.
BIOLOGICAL REVIEWS
(2021)
Article
Clinical Neurology
Jelena Ilic Zivojinovic, Katarina Djurdjevic, Ivo Bozovic, Giovanni Meola, Marina Peric, Ana Azanjac Arsic, Ivana Basta, Vidosava Rakocevic-Stojanovic, Stojan Peric
Summary: This cross-sectional study aimed to evaluate COVID-19 infection and vaccination rate in patients with myotonic dystrophy type 1 (DM1). The study found that 40.4% of DM1 patients were infected with COVID-19, with around 14% requiring hospitalization. Vaccination was highly effective in preventing severe COVID-19 cases, as none of the vaccinated patients experienced severe symptoms compared to 20.8% of unvaccinated patients.
NEUROLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mari Carmen Alvarez-Abril, Irma Garcia-Alcover, Jordi Colonques-Bellmunt, Raquel Garijo, Manuel Perez-Alonso, Ruben Artero, Arturo Lopez-Castel
Summary: This study demonstrates that boldine, a natural alkaloid identified in a large-scale Drosophila-based pharmacological screening, can modify disease phenotypes in several DM1 models. The most significant effects include consistent reduction in nuclear RNA foci, a dynamic molecular hallmark of the disease, and noteworthy anti-myotonic activity. These findings position boldine as an attractive new candidate for therapy development in DM1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Adriana Costa, Ana C. Cruz, Filipa Martins, Sandra Rebelo
Summary: Protein phosphorylation alterations in DM1 contribute to the various manifestations and symptoms of the disease. A systematic review identified abnormal levels of protein kinases, phosphatases, and phosphoproteins in DM1. Multiple signaling pathways involved in cell functions such as glucose metabolism, cell cycle, myogenesis, and apoptosis were impaired in DM1 samples, explaining the complexity and diverse symptoms of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Masayuki Nakamori, Hideki Mochizuki
Summary: Recent technological advancements in genetic analysis have led to the consecutive discovery and elucidation of repeat expansion disorders, which are caused by abnormal expansion of repeat sequences in the genome. While radical cures for these disorders are still lacking, research is exploring therapeutic approaches targeting repeat DNA, the root cause of these disorders. Small molecules that target abnormally expanded repeat sequences have shown promise in shortening them, potentially leading to groundbreaking therapeutic drugs for repeat expansion disorders.
MOVEMENT DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Hayato Fukusumi, Kazuyuki Togo, Miho Sumida, Masayuki Nakamori, Satoshi Obika, Kousuke Baba, Tomoko Shofuda, Daisuke Ito, Hideyuki Okano, Hideki Mochizuki, Yonehiro Kanemura
Summary: This study found increased accumulation of alpha-synuclein in DA neurons derived from PARK4 patients, but the accumulation disappeared over time. An SNCA-specific antisense oligonucleotide could reduce alpha-synuclein levels during the accumulation stage.
Article
Chemistry, Organic
Victor A. Jaffett, Jhewelle N. Fitz-Henley, Muhammad M. Khalifa, Ilia A. Guzei, Jennifer E. Golden
Summary: An efficient synthetic route was developed for the enantioselective synthesis of a variety of pyrrolopyrazinoquinazolinones through a domino reaction and intramolecular cyclization. This method can achieve high yields of pyrazinoquinazolinones and easily separate diastereomeric pairs.
Article
Neurosciences
Yuhei Hasuike, Hana Tanaka, Terence Gall-Duncan, Mustafa Mehkary, Kazuhiko Nakatani, Christopher E. Pearson, Shoji Tsuji, Hideki Mochizuki, Masayuki Nakamori
Summary: This study demonstrates the therapeutic potential of using repeat contracting small molecules, such as naphthyridine-azaquinolone (NA), to treat repeat expansion disorders like Dentatorubral-pallidoluysian atrophy (DRPLA). The long-term intracerebroventricular infusion of NA leads to repeat contraction, reduces mutant ATN1 aggregation, and improves motor phenotype in a murine model of DRPLA.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Cell Biology
Amit Laxmikant Deshmukh, Marie-Christine Caron, Mohiuddin Mohiuddin, Stella Lanni, Gagan B. Panigrahi, Mahreen Khan, Worrawat Engchuan, Natalie Shum, Aisha Faruqui, Peixiang Wang, Ryan K. C. Yuen, Masayuki Nakamori, Kazuhiko Nakatani, Jean-Yves Masson, Christopher E. Pearson
Summary: Ongoing inchworm-like CAG and CGG repeat expansions in brains may drive neurological disorders like Huntington's disease, fragile X syndrome, and autism. The FAN1 nuclease plays a key role in modifying hyperexpansion rates through binding, dimerizing, and cleaving slipped DNAs. Rare FAN1 variants are associated with individuals with autism and CGG/CCG expansions. Slip-outs of CGG/CCG repeats show exo-nuclease pauses.
Article
Biochemistry & Molecular Biology
Yuhei Hasuike, Hideki Mochizuki, Masayuki Nakamori
Summary: Myotonic dystrophy is a genetic disorder affecting multiple organs with clinical similarities to aging. Cellular senescence plays a key role in the pathogenesis of myotonic dystrophy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Yuhei Hasuike, Hideki Mochizuki, Masayuki Nakamori
Summary: This study aims to investigate the mechanism of cellular senescence caused by CUG(exp) RNA in myotonic dystrophy type 1 (DM1). The study found that CUG(exp) RNA expression leads to mitochondrial dysfunction, excessive production of reactive oxygen species, and DNA damage and response, resulting in an increase in senescence-related factors and secreted mediators.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Mougina K. Eltahir, Masayuki Nakamori, Satoshi Hattori, Takashi Kimura, Hideki Mochizuki, Seiichi Nagano
Summary: This study successfully established a neuronal model for DM1 and found faster degeneration, aberrant splicing, and nuclear RNA foci in DM1 hiNeurons. They also tested the effectiveness of two drugs and found that they reduced the number of RNA foci and corrected splicing abnormalities. This research provides a valuable tool and direction for further understanding and treating DM1.
Article
Clinical Neurology
Masayuki Nakamori
Summary: Myotonic dystrophy is the most common muscular dystrophy in adults, affecting skeletal muscle, cardiac and smooth muscle, as well as the central nervous system, endocrine organs, and eyes. It is caused by abnormal genomic expansion of tandem repeats, resulting in abnormal mRNA that exerts toxic effects on cellular processes. This review discusses the molecular pathomechanisms mediated by expanded-repeat-RNA in myotonic dystrophy.
NEUROLOGY AND CLINICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Anissa Souidi, Masayuki Nakamori, Monika Zmojdzian, Teresa Jagla, Yoan Renaud, Krzysztof Jagla
Summary: Myotonic dystrophy type 1 (DM1) is a common muscular dystrophy in adults caused by excessive expansion of noncoding CTG repeats, leading to dysfunction of RNA-binding factors and affecting alternative splicing, processing, and stability of muscular and cardiac transcripts. This study explores the role of miR-1 in cardiac dysfunction in DM1 using Drosophila DM1 models. It is found that down-regulation of miR-1 in the heart results in dilated cardiomyopathy (DCM) and Multiplexin (Mp) is identified as a new cardiac miR-1 target involved in DM1-associated DCM.
Article
Clinical Neurology
Naoki Suzuki, Madoka Mori-Yoshimura, Masahisa Katsuno, Masanori P. Takahashi, Satoshi Yamashita, Yasushi Oya, Atsushi Hashizume, Shinichiro Yamada, Masayuki Nakamori, Rumiko Izumi, Masaaki Kato, Hitoshi Warita, Maki Tateyama, Hiroshi Kuroda, Ryuta Asada, Takuhiro Yamaguchi, Ichizo Nishino, Masashi Aoki
Summary: This study evaluated the safety and efficacy of oral supplementation of aceneuramic acid in patients with GNE myopathy. The results showed that the SA-ER group had a greater change in upper limb muscle strength compared to the placebo group at 48 weeks, and no other serious adverse effects were observed.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Terence Gall-Duncan, Jennifer Luo, Carla-Marie Jurkovic, Laura A. Fischer, Kyota Fujita, Amit L. Deshmukh, Rachel J. Harding, Stephanie Tran, Mustafa Mehkary, Vanessa Li, David E. Leib, Ran Chen, Hikari Tanaka, Amanda G. Mason, Dominique Levesque, Mahreen Khan, Mortezaali Razzaghi, Tanya Prasolava, Stella Lanni, Nozomu Sato, Marie-Christine Caron, Gagan B. Panigrahi, Peixiang Wang, Rachel Lau, Arturo Lopez Castel, Jean-Yves Masson, Lynette Tippett, Clinton Turner, Maria Spies, Albert R. La Spad, Eric I. Campos, Maurice A. Curtis, Francois-Michel Boisvert, Richard L. M. Faull, Beverly L. Davidson, Masayuki Nakamori, Hitoshi Okazawa, Marc S. Wold, Christopher E. Pearson
Summary: Expansions of repeat DNA tracts can cause diseases and their progression in the brain. Two types of ssDNA-binding complexes, RPA and Alt-RPA, have different expressions and functions in the repair and expansion of slipped-DNAs, potentially impacting disease development.
Article
Genetics & Heredity
Madoka Mori-Yoshimura, Naoki Suzuki, Masahisa Katsuno, Masanori P. Takahashi, Satoshi Yamashita, Yasushi Oya, Atsushi Hashizume, Shinichiro Yamada, Masayuki Nakamori, Rumiko Izumi, Masaaki Kato, Hitoshi Warita, Maki Tateyama, Hiroshi Kuroda, Ryuta Asada, Takuhiro Yamaguchi, Ichizo Nishino, Masashi Aoki
Summary: In a study on GNE myopathy, oral administration of aceneuramic acid showed potential in slowing disease progression. Comparison of muscle strength and function over 48 weeks revealed better efficacy in the group receiving aceneuramic acid compared to placebo. No clinically significant adverse events or safety concerns were observed.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Clinical Neurology
Masayuki Nakamori, Hiroshi Shimizu, Kotaro Ogawa, Yuhei Hasuike, Takashi Nakajima, Hidetoshi Sakurai, Toshiyuki Araki, Yukinori Okada, Akiyoshi Kakita, Hideki Mochizuki
Summary: Central nervous system symptoms in patients with myotonic dystrophy significantly affect their quality of life. A study on the genetic, epigenetic, and transcriptomic characteristics of cortical neurons, white matter glial cells, and spinal motor neurons provides new insights into the pathogenesis of myotonic dystrophy.
BRAIN COMMUNICATIONS
(2022)
Review
Clinical Neurology
Masayuki Nakamori
Summary: Myotonic dystrophy is the most common form of muscular dystrophy in adults, caused by unstable genomic expansions of CTG or CCTG repeats. Therapeutic approaches targeting toxic RNA include antisense oligonucleotides and small molecules.
NEUROLOGY AND CLINICAL NEUROSCIENCE
(2022)