Article
Genetics & Heredity
Mary L. Vo, Tess Levy, Shenela Lakhani, Chengbing Wang, M. Elizabeth Ross
Summary: This study established the correct molecular diagnosis of adult-onset NPC in a patient initially diagnosed with SCA. Whole exome sequencing and other cellular and biochemical methods were used to identify the genetic variants causing NPC in the patient. This suggests that using whole exome sequencing for the diagnosis of genetic diseases is justified.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Clinical Neurology
Tatiana Bremova-Ertl, Jens Claassen, Tomas Foltan, Jordi Gascon-Bayarri, Paul Gissen, Andreas Hahn, Anhar Hassan, Anita Hennig, Simon A. Jones, Miriam Kolnikova, Kyriakos Martakis, Jan Raethjen, Uma Ramaswami, Reena Sharma, Susanne A. Schneider
Summary: The study found that N-acetyl-L-leucine (NALL) has a significant and clinically meaningful improvement in symptoms, functioning, and quality of life in pediatric and adult Niemann-Pick disease type C (NPC) patients, with a favorable safety profile. However, the therapeutic effect was lost after a 6-week washout period.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Nikola Kresojevic, Valerija Dobricic, Milica Jecmenica Lukic, Aleksandra Tomic, Igor Petrovic, Natasa Dragasevic, Ivana Perovic, Ana Marjanovic, Marija Brankovic, Milena Jankovic, Ivana Novakovic, Marina Svetel, Vladimir S. Kostic
Summary: Niemann Pick type C is a neuro-visceral disease with clinical features depending on the age at onset. This study screened for gene changes in 150 patients and identified novel NPC1 gene variants. The results showed that movement disorders were common initial symptoms in early onset cases, while psychiatric or cognitive disturbances were more prominent in later onset cases.
JOURNAL OF NEUROLOGY
(2022)
Article
Genetics & Heredity
Neng-Li Wang, Lian Chen, Yi Lu, Xin-Bao Xie, Jing Lin, Kuerbanjiang Abuduxikuer, Jian-She Wang
Summary: This study found that the presence of vacuolated Kupffer cells can raise a high clinical suspicion of NP-C in neonatal cholestatic infants, especially in those with splenomegaly. The ratio of positive diagnosis of NP-C was significantly higher in neonatal cholestatic infants with both vacuolated Kupffer cells and splenomegaly compared to those without these features.
FRONTIERS IN GENETICS
(2022)
Article
Pediatrics
Dror Kraus, Huda Abdelrahim, Orith Waisbourd-Zinman, Elena Domin, Avraham Zeharia, Orna Staretz-Chacham
Summary: Niemann-Pick disease type C (NPC) is a rare neuro-visceral lipid storage disease. This study found that elevated serum alpha-fetoprotein levels could potentially be a useful marker for diagnosing NPC-associated liver disease in infants.
Article
Developmental Biology
Wei-Chia Tseng, Ana J. Johnson Escauriza, Chon-Hwa Tsai-Morris, Benjamin Feldman, Ryan K. Dale, Christopher A. Wassif, Forbes D. Porter
Summary: NPC is a rare, fatal neurodegenerative lysosomal disease caused by mutations in NPC1 or NPC2, resulting in the accumulation of cholesterol and other lipids in the lysosome and reduction in cellular cholesterol bioavailability.
Review
Genetics & Heredity
Marisa Encarnacao, Isaura Ribeiro, Hugo David, Maria Francisca Coutinho, Dulce Quelhas, Sandra Alves
Summary: Niemann-Pick type C is a rare neuro-visceral psychiatric disease caused by pathogenic variants in NPC1 or NPC2 genes. Diagnosis is challenging due to the rarity of the disease and its diverse clinical phenotypes. Understanding splicing variants in NPC1 and NPC2 genes can improve diagnosis.
Review
Clinical Neurology
Susanne A. Schneider, Sabina Tahirovic, John Hardy, Michael Strupp, Tatiana Bremova-Ertl
Summary: Research suggests a high proportion of late-onset neurodegenerative diseases in families with NPC mutations. 19 cases in the literature have shown individuals with heterozygous NPC mutations presenting with neurodegenerative diseases such as PD, atypical parkinsonism, dystonia, or dementia.
JOURNAL OF NEUROLOGY
(2021)
Article
Medicine, Research & Experimental
Denzil Furtado, Christina Cortez-Jugo, Ya Hui Hung, Ashley I. Bush, Frank Caruso
Summary: Researchers successfully used NPC1-encoded mRNA to combat protein insufficiency and pathogenic phenotype caused by biallelic NPC1 mutations, achieving treatment for the rare disease NP-C1. The gene engineering strategies greatly improved the expression efficiency of the mRNA.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Rita Pepponi, Roberta De Simone, Chiara De Nuccio, Sergio Visentin, Andrea Matteucci, Antonietta Bernardo, Patrizia Popoli, Antonella Ferrante
Summary: In this study, it was found that increasing adenosine levels may represent a new therapeutic approach for NPC. Experimental evidence from animal models and patient cells indicates that increasing adenosine levels by inhibiting the equilibrative nucleoside transporter (ENT1) can reduce lipid accumulation and improve mitochondrial deficits in NPC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Insung Kang, Je Min Yoo, Donghoon Kim, Juhee Kim, Myung Keun Cho, Seung-Eun Lee, Dong Jin Kim, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Nari Shin, Soon Won Choi, Young-Ho Lee, Han Seok Ko, Seokmin Shin, Byung Hee Hong, Kyung-Sun Kang
Summary: Graphene quantum dots (GQDs) show promise as a potential therapeutic agent for Niemann-Pick disease type C (NPC) by reducing cholesterol aggregation in lysosomes, promoting autophagy, and inhibiting Purkinje cell loss in the cerebellum. Their ability to alleviate impaired functions in NPC highlights the potential of GQDs for treating NPC and related disorders.
Article
Oncology
Yusei Yamada, Madoka Fukaura-Nishizawa, Asami Nishiyama, Akira Ishii, Tatsuya Kawata, Aina Shirakawa, Mayuko Tanaka, Yuki Kondo, Toru Takeo, Naomi Nakagata, Toru Miwa, Hiroki Takeda, Yorihisa Orita, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Takahiro Seki, Yuki Kurauchi, Hiroshi Katsuki, Katsumi Higaki, Kentaro Minami, Naoki Yoshikawa, Ryuji Ikeda, Muneaki Matsuo, Tetsumi Irie, Yoichi Ishitsuka
Summary: This study investigates the relationship between the formation of cyclodextrin (CD) and unesterified cholesterol (UC) complexes and their therapeutic effectiveness. The findings suggest that the solubility and molecular mechanisms of CD influence the formation and complexation capability of these complexes. The ability of CD derivatives to form 1:1 and 2:1 complexes is correlated with their therapeutic efficacy and toxicity, respectively. These findings highlight the importance of optimizing the molecular structure of CDs to overcome current treatment dilemmas.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Yusei Yamada, Madoka Fukaura-Nishizawa, Asami Nishiyama, Akira Ishii, Tatsuya Kawata, Aina Shirakawa, Mayuko Tanaka, Yuki Kondo, Toru Takeo, Naomi Nakagata, Toru Miwa, Hiroki Takeda, Yorihisa Orita, Keiichi Motoyama, Taishi Higashi, Hidetoshi Arima, Takahiro Seki, Yuki Kurauchi, Hiroshi Katsuki, Katsumi Higaki, Kentaro Minami, Naoki Yoshikawa, Ryuji Ikeda, Muneaki Matsuo, Tetsumi Irie, Yoichi Ishitsuka
Summary: This study found that cyclodextrins can be used to treat Niemann-Pick disease type C (NPC), but concerns about ototoxicity exist. By optimizing the molecular structure of cyclodextrins, this study suggests a way to overcome this dilemma.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Endocrinology & Metabolism
Dominika Sitarska, Anna Tylki-Szymanska, Agnieszka Lugowska
Summary: Niemann-Pick type C (NPC) disease is a genetically determined neurodegenerative metabolic disease caused by impaired cholesterol transport. Treatment focuses on slowing disease progression, with the only registered drug being Miglustat.
METABOLIC BRAIN DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Antonietta Bernardo, Chiara De Nuccio, Sergio Visentin, Alberto Martire, Luisa Minghetti, Patrizia Popoli, Antonella Ferrante
Summary: Niemann-Pick type C (NPC) disease is a neurovisceral disorder that mainly affects the liver and brain, caused by mutations in genes coding for proteins involved in cholesterol transport. NPC leads to the accumulation of unesterified cholesterol in lysosomes, affecting mitochondrial function and leading to neurodegeneration and myelin defects in the brain. Emerging pharmacological strategies targeting A(2A) adenosine receptor stimulation show promise for NPC therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Tim W. Rattay, Maximilian Voelker, Maren Rautenberg, Christoph Kessler, Isabel Wurster, Natalie Winter, Tobias B. Haack, Tobias Lindig, Holger Hengel, Matthis Synofzik, Rebecca Schule, Peter Martus, Ludger Schoels
Summary: This study explores early changes in the most common subtype of hereditary spastic paraplegia, SPG4, and identifies subclinical markers of disease activity in the prodromal stage. The findings suggest that certain clinical signs, such as increased reflexes and muscle weakness, may be more frequent in individuals who carry the genetic mutation associated with SPG4.
Article
Clinical Neurology
Elizabeth Finger, Rubina Malik, Martina Bocchetta, Kristy Coleman, Caroline Graff, Barbara Borroni, Mario Masellis, Robert Laforce, Caroline Greaves, Lucy L. Russell, Rhian S. Convery, Arabella Bouzigues, David M. Cash, Markus Otto, Matthis Synofzik, James B. Rowe, Daniela Galimberti, Pietro Tiraboschi, Robert Bartha, Christen Shoesmith, Maria Carmela Tartaglia, John C. van Swieten, Harro Seelaar, Lize C. Jiskoot, Sandro Sorbi, Chris R. Butler, Alexander Gerhard, Raquel Sanchez-Valle, Alexandre de Mendonca, Fermin Moreno, Rik Vandenberghe, Isabelle Le Ber, Johannes Levin, Florence Pasquier, Isabel Santana, Jonathan D. Rohrer, Simon Ducharme
Summary: This study investigates the hypothesis that genetic mutations causing frontotemporal dementia (FTD) have neurodevelopmental consequences. The researchers examined brain structure and function in young adult mutation carriers and found differences between preclinical mutation carriers and familial non-carriers at a mean age of 26 years. These findings have implications for therapeutic interventions and further studies on early pathophysiologic processes in FTD.
Editorial Material
Biochemistry & Molecular Biology
Annemieke Aartsma-Rus, Willeke van Roon-Mom, Marlen Lauffer, Christine Siezen, Britt Duijndam, Tineke Coenen-de Roo, Rebecca Schuele, Matthis Synofzik, Holm Graessner
Summary: Splice-modulating antisense oligonucleotides (ASOs) provide treatment options for rare neurological diseases with rare mutations, and patient-specific ASOs need to be developed. The 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop and treat eligible patients with patient-specific ASOs in Europe and the Netherlands, respectively, under a named patient setting.
Letter
Clinical Neurology
Zofia Fleszar, Claudia Dufke, Marc Sturm, Rebecca Schuele, Ludger Schoels, Tobias B. Haack, Matthis Synofzik
JOURNAL OF NEUROLOGY
(2023)
Article
Health Care Sciences & Services
M. Grobe-Einsler, J. Faber, A. Taheri, J. Kybelka, J. Raue, J. Volkening, F. Helmhold, M. Synofzik, T. Klockgether
Summary: Ataxias refer to a group of movement disorders, characterized by progressive loss of balance, impaired coordination, and speech disturbance, resulting in a significant reduction in quality of life. Although speech disturbance can be clinically diagnosed, there is a lack of objective methods for assessing its severity. Through the analysis of 71 sets of speech recordings from ataxia patients, an automated classification system was developed. This system correctly predicted the expert ratings of speech disturbance in 80% of cases, demonstrating the feasibility of computer-assisted voice analysis for automated assessment of speech disturbance severity.
NPJ DIGITAL MEDICINE
(2023)
Article
Clinical Neurology
Curtiss A. Chapman, Maryna Polyakova, Karsten Mueller, Christopher Weise, Klaus Fassbender, Klaus Fliessbach, Johannes Kornhuber, Martin Lauer, Sarah Anderl-Straub, Albert Ludolph, Johannes Prudlo, Anja Staiger, Matthis Synofzik, Jens Wiltfang, Lina Riedl, Janine Diehl-Schmid, Markus Otto, Adrian Danek, Gesa Hartwigsen, Matthias L. Schroeter
Summary: Understanding the relationship between brain structure and language behavior in primary progressive aphasia is crucial for understanding the pathomechanisms of these diseases. This study found that there are networks of language task-associated brain regions, some of which show atrophy and others do not, suggesting regions of future network disruption and providing insights into task deficits beyond atrophied cortex.
BRAIN COMMUNICATIONS
(2023)
Article
Cell Biology
David Mengel, Isabel G. Wellik, Kristen H. Schuster, Sabrina I. Jarrah, Madeleine Wacker, Naila S. Ashraf, Gulin Oez, Matthis Synofzik, Maria do Carmo Costa, Hayley S. Mcloughlin
Summary: The study found that blood NfL levels gradually increase in a SCA3 mouse model during disease progression, and are associated with motor deficits and neurometabolite abnormalities related to ataxia. This further supports the utility of blood NfL as a peripheral biomarker for neurodegenerative diseases, and provides a timeline for different measures of SCA3 pathogenesis.
DISEASE MODELS & MECHANISMS
(2023)
Letter
Clinical Neurology
Holger Hengel, David Pellerin, Carlo Wilke, Zofia Fleszar, Bernard Brais, Tobias Haack, Andreas Traschuetz, Ludger Schoels, Matthis Synofzik
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Andreas Traschuetz, Felix Heindl, Muhammad Bilal, Annette M. Hartmann, Claudia Dufke, Olaf Riess, Andreas Zwergal, Dan Rujescu, Tobias Haack, Matthis Synofzik, Michael Strupp
Summary: Bilateral vestibulopathy is a chronic neurological disorder with unknown monogenic cause. This study identifies replication factor complex subunit 1 repeat expansions as a common cause of the disease and provides detailed characterization of its features and progression.
Article
Biology
Federico Zilio, Javier Gomez-Pilar, Ujwal Chaudhary, Stuart Fogel, Tatiana Fomina, Matthis Synofzik, Ludger Schols, Shumei Cao, Jun Zhang, Zirui Huang, Niels Birbaumer, Georg Northoff
Summary: EEG-based measures such as power-law exponent (PLE) and Lempel-Ziv complexity (LZC) can be used to identify biomarkers associated with complete locked-in syndrome (CLIS), allowing for better treatment and communication options.
COMMUNICATIONS BIOLOGY
(2023)
Article
Clinical Neurology
Catherine Ashton, Elisabetta Indelicato, David Pellerin, Guillemette Clement, Matt C. Danzi, Marie-Josee Dicaire, Celine Bonnet, Henry Houlden, Stephan Zuechner, Matthis Synofzik, Phillipa J. Lamont, Mathilde Renaud, Sylvia Boesch, Bernard Brais
Summary: Ashton C et al report a retrospective multi-centre cohort study of 34 patients from Canada, France, Austria and Australia with spinocerebellar ataxia 27B. The study describes the common feature of episodic ataxia and other episodic features, and also highlights the ineffectiveness of acetazolamide in these patients.
BRAIN COMMUNICATIONS
(2023)
Article
Neurosciences
Filippo Santorelli, Hayley McLoughlin, Justin Wolter, Daniele Galatolo, Matthis Synofzik, David Mengel, Puneet Opal
Summary: The Ataxia Global Initiative (AGI) aims to facilitate clinical trial readiness for hereditary ataxias by addressing the lack of objective measures for disease study and treatment evaluation. The AGI fluid biomarker working group has developed protocols to standardize sampling and storage of biomarkers for both human and mouse studies, with the goal of reducing variability and improving statistical power in downstream analysis. Emphasis has been placed on harmonizing minimal biological sample collection and storage, while optional protocols are available for advanced biofluid processing and storage.
Correction
Clinical Neurology
Holger Hengel, Peter Martus, Jennifer Faber, Paola Giunti, Hector Garcia-Moreno, Nita Solanky, Thomas Klockgether, Kathrin Reetz, Bart P. van de Warrenburg, Magda M. Santana, Patrick Silva, Ines Cunha, Luis Pereira de Almeida, Dagmar Timmann, Jon Infante, Jeroen de Vries, Manuela Lima, Paula Pires, Khalaf Bushara, Heike Jacobi, Chiadi Onyike, Jeremy D. Schmahmann, Jeannette Huebener-Schmid, Matthis Synofzik, Ludger Schoels
JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Maresa Buchholz, Niklas Weber, Anika Raedke, Jennifer Faber, Tanja Schmitz-Huebsch, Heike Jacobi, Feng Xie, Thomas Klockgether, Bernhard Michalowsky
Summary: The study confirmed an acceptable, reliable, valid, and responsive EQ-5D-3L in SCA patients, measuring HRQoL adequately, besides well-established clinical instruments.
