Review
Neurosciences
LiDan Hu, Shanshan Mao, Li Lin, Guannan Bai, Bingjie Liu, Jianhua Mao
Summary: This review provides an overview of the genetic and biochemical studies on stress granules in SMA and ALS, and discusses the mechanisms through which stress granules are involved in the pathogenesis of these diseases. It also summarizes the current therapies and proposes potential targets on stress granules for future interventions of SMA and ALS.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Behavioral Sciences
Jin-Yue Li, Yi Dai, Xiao-Han Sun, Hai-tao Ren, Dong-chao Shen, Xun-Zhe Yang, Ming-Sheng Liu, Li-Ying Cui
Summary: This study aimed to identify potential biomarkers for monitoring and diagnosing adult SMA patients and sporadic ALS patients. The results showed that the levels of serum Cr, CSF NFL, and CSF pNFH were significantly higher in ALS patients compared to adult SMA patients. CSF NFL and pNFH may be useful biomarkers for differential diagnosis of adult SMA and ALS.
BRAIN AND BEHAVIOR
(2023)
Article
Chemistry, Analytical
Chunhua Zhang, Zhuo Li, Miaomiao Chen, Zhiqing Hu, Lingqian Wu, Miaojin Zhou, Desheng Liang
Summary: The SMA-Cas12a-strip assay is a simple, cost-effective, highly sensitive, and specific detection method for SMA patients, with 100% sensitivity and specificity validated with clinical samples, and a short turnaround time.
Review
Clinical Neurology
David Brenner, Axel Freischmidt
Summary: ALS genetics research is highly dynamic and intriguing, with the discovery of numerous new ALS-associated genes and pathomechanisms. Recent findings include potential and risk genes, as well as new risk loci. Cell type and functional enrichment analyses have shed light on the genetic basis of selective motor neuron vulnerability in ALS, and major insights have been gained regarding known ALS genes and proteins. The understanding of ALS genetics and molecular basis has advanced significantly in the past years, leading to the development of novel gene-specific therapies for sporadic ALS and genetic subtypes.
CURRENT OPINION IN NEUROLOGY
(2022)
Article
Clinical Neurology
Christian Schneider, Meike K. Wassermann, Nicolai B. Grether, Gereon R. Fink, Gilbert Wunderlich, Helmar C. Lehmann
Summary: The study evaluated the organization and short-term changes of motor units in adult patients with spinal muscular atrophy (SMA) treated with nusinersen, finding significantly lower motor unit numbers in patients with SMA and a moderate to strong correlation between electrophysiological measures and clinical scores.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Annapoorna Kannan, Juliana Cuartas, Pratik Gangwani, Dana Branzei, Laxman Gangwani
Summary: A mutation in the SETX gene causes ALS4, a neuromuscular disorder characterized by motor neuron degeneration, muscle weakness, and atrophy. We discovered that ZPR1, a zinc finger protein, plays a critical role in R-loop resolution by recruiting SETX onto R-loops. Deficiency of ZPR1 disrupts R-loop resolution and leads to increased R-loop accumulation. Furthermore, the interaction between SETX and ZPR1 is disrupted in ALS4 patients, resulting in elevated R-loop resolution activity. Modulation of ZPR1 levels can regulate R-loop accumulation and rescue the pathogenic R-loop phenotype in ALS4 patient cells.
Article
Neurosciences
Miguel Oliveira Santos, Marta Gromicho, Ana Pronto-Laborinho, Mamede de Carvalho
Summary: Amyotrophic lateral sclerosis (ALS) and myopathy are part of a genetic syndrome called multisystem proteinopathy. They can occur together or separately, and may be associated with other clinical features. This study aims to characterize three sporadic ALS patients, one with concurrent myopathy and two with previous myopathy diagnoses before motor neuron signs emerged. These cases suggest a potential connection between skeletal muscle degeneration and motor neuron damage.
Article
Multidisciplinary Sciences
Akiko Hirotsu, Mariko Miyao, Kenichiro Tatsumi, Tomoharu Tanaka
Summary: In septic patients, neuroinflammation plays a crucial role in central nervous system disorders. However, the impact of sepsis on the spinal cord remains unclear. This study demonstrated that sepsis induces acute neuroinflammation in the spinal cord, characterized by microglial activation and upregulation of pro-inflammatory cytokines, leading to severe neuronal ischemia and white matter edema.
Review
Neurosciences
Brunhilde Wirth
Summary: The review highlights the challenging journey from gene discovery to therapy in spinal muscular atrophy (SMA), emphasizing the importance of perseverance in uncovering the biological mechanisms of the disease. Despite the impressive improvements seen with three therapeutic strategies in SMA, there are still many unanswered questions that need to be addressed as discussed in the review.
TRENDS IN NEUROSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Elisa Duranti, Chiara Villa
Summary: ALS is a fatal disease characterized by the loss of motor neurons, leading to muscle damage and paralysis. Muscle research plays a crucial role in understanding the molecular mechanisms and developing treatments for this disease.
Article
Clinical Neurology
Nadja Ratia, Edouard Palu, Hanna Lantto, Emil Ylikallio, Ritva Luukkonen, Anu Suomalainen, Mari Auranen, Paivi Piirila
Summary: In cardiopulmonary exercise test, subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Maria Isabel Moreno-Gambin, Jose Tembl, Miguel Mazon, Antonio Jose Canada-Martinez, Luis Marti-Bonmati, Teresa Sevilla, Juan F. Vazquez-Costa
Summary: The absence of nigrosome 1 is associated with male sex, UMN impairment, and shorter survival in ALS patients. This suggests that constitutional factors and the degree of pyramidal involvement are related to substantia nigra involvement in ALS, serving as a marker of multisystem degeneration and poor prognosis.
JOURNAL OF NEUROLOGY
(2022)
Review
Neurosciences
Hui Wang, LiPing Guan, Min Deng
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. The causes of ALS are not fully understood but genetic factors play a role in about 10% of cases. Recent studies have identified over 40 ALS genes, which contribute to a better understanding of the disease and the development of potential treatments.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Medicine, Research & Experimental
Audrey M. Winkelsas, Christopher Grunseich, George G. Harmison, Katarzyna Chwalenia, Carlo Rinaldi, Suzan M. Hammond, Kory Johnson, Melissa Bowerman, Sukrat Arya, Kevin Talbot, Matthew J. Wood, Kenneth H. Fischbeck
Summary: Research shows that ASOs targeting the 50 end of SMN2 can increase SMN mRNA and protein levels by inhibiting SMN2 mRNA decay. Combining 50 UTR ASO with SSO can elevate SMN levels beyond those achieved with SSO alone, offering a new therapeutic target for SMA.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Clinical Neurology
Daniel Natera-de Benito, Sergio Aguilera-Albesa, Laura Costa-Comellas, Mar Garcia-Romero, Maria Concepcion Miranda-Herrero, Julia Rubies Olives, Oscar Garcia-Campos, Elena Martinez del Val, Maria Josefa Martinez Garcia, Inmaculada Medina Martinez, Ramon Cancho-Candela, Miguel A. Fernandez-Garcia, Samuel Ignacio Pascual-Pascual, David Gomez-Andres, Andres Nascimento
Summary: This study described the clinical characteristics and outcomes of COVID-19 in 29 children with neuromuscular disorders, showing that no severe complications were observed and the majority of cases were asymptomatic or mild.
JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
David R. R. Lynch, Melanie P. P. Chin, Sylvia Boesch, Martin B. B. Delatycki, Paola Giunti, Angie Goldsberry, J. Chad Hoyle, Caterina Mariotti, Katherine D. D. Mathews, Wolfgang Nachbauer, Megan O'Grady, Susan Perlman, S. H. Subramony, George Wilmot, Theresa Zesiewicz, Colin J. J. Meyer
Summary: The study evaluated the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia. The results showed a persistent benefit of omaveloxolone treatment on disease course in Friedreich's ataxia.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Jan L. De Bleecker, Kristl G. Claeys, Stephanie Delstanche, Vinciane Van Parys, Jonathan Baets, Sebastien Tilleux, Gauthier Remiche
Summary: This retrospective study analyzed medical records of hATTR amyloidosis patients treated with patisiran between July 1, 2018 and February 1, 2021. The results showed that most patients had stable or improved neurological and cardiological assessments after patisiran treatment.
ACTA NEUROLOGICA BELGICA
(2023)
Article
Clinical Neurology
Pedro Ervilha Pereira, Nika Schuermans, Antoon Meylemans, Pontus LeBlanc, Lauren Versluys, Katie E. E. Copley, Jack D. D. Rubien, Christopher Altheimer, Myra Peetermans, Elke Debackere, Olivier Vanakker, Sandra Janssens, Jonathan Baets, Kristof Verhoeven, Martin Lammens, Sofie Symoens, Boel De Paepe, Sami J. J. Barmada, James Shorter, Jan L. L. De Bleecker, Elke Bogaert, Bart Dermaut
Summary: This study identified a TDP-43(p.Trp385IlefsTer10) mutation in a family, which led to the presence of TDP-43-positive inclusions in muscle cells and the development of autosomal dominant rimmed vacuole myopathy. The mutation was found to increase the aggregation propensity of TDP-43, but it was not associated with ALS and FTD.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Thomas Gasser
Summary: After years of research and setbacks, gene therapies have achieved undeniable success by directly modifying genetic information on the DNA or RNA level. Both ex vivo strategies, manipulating patient cells outside the body, and in vivo approaches have been successful. In addition to gene supplementation, the use of the CRISPR-Cas9 system for altering nuclear DNA sequences and interfering with the transcriptional process on the RNA level can also be considered as gene therapies in a broad sense.
FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE
(2023)
Review
Clinical Neurology
Ullrich Wuellner, Per Borghammer, Chi-un Choe, Ilona Csoti, Bjorn Falkenburger, Thomas Gasser, Paul Lingor, Peter Riederer
Summary: The heterogeneity of Parkinson's disease presents challenges for future research and therapeutic design. Various pathophysiological concepts and mechanisms, including alpha-synuclein misfolding, oxidative stress, and microbial agents, may contribute to the development of PD. The unresolved heterogeneity of PD has hindered previous clinical trials, highlighting the need for personalized therapeutic approaches.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Review
Clinical Neurology
Thomas Gasser
Summary: The identification of disease-causing mutations or strong risk factors for Parkinson's disease in specific genes has led to a better understanding of disease pathogenesis. Many gene and mutation-specific targeted disease-modifying treatments are being developed and studied. Therefore, it is important to raise awareness and offer genetic testing to patients considering innovative trials.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Clinical Neurology
Pierre-Emmanuel Sugier, Elise A. Lucotte, Cloe Domenighetti, Matthew H. Law, Mark M. Iles, Kevin Brown, Christopher Amos, James D. McKay, Rayjean J. Hung, Mojgan Karimi, Delphine Bacq-Daian, Anne Boland-Auge, Robert Olaso, Jean-francois Deleuze, Fabienne Lesueur, Evgenia Ostroumova, Ausrele Kesminiene, Florent de Vathaire, Pascal Guenel, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Sandeep Grover, Patrick May, Dheeraj R. Bobbili, Milena Radivojkov-Blagojevic, Peter Lichtner, Andrew B. Singleton, Dena G. Hernandez, Connor Edsall, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B. Deutschlaender, Georges M. Hadjigeorgiou, Efthimios Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Pierre Kolber, Bart P. C. van de Warrenburg, Bastiaan R. Bloem, Jan Aasly, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J. Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Monica Diez-Fairen, Karin Wirdefeldt, Nancy Pedersen, Caroline Ran, Andrea C. Belin, Andreas Puschmann, Emil Ygland Roedstroem, Carl E. Clarke, Karen E. Morrison, Manuela Tan, Dimitri Krainc, Lena F. Burbulla, Matt J. Farrer, Rejko Kruger, Thomas Gasser, Manu Sharma, Therese Truong, Alexis Elbaz
Summary: By using genome-wide association studies, this study found that Parkinson's disease (PD) is genetically correlated with melanoma and prostate cancer, while it is inversely correlated with ovarian cancer. These findings suggest that pleiotropic genes contribute to the association between PD and specific cancers.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Lorenzo Nanetti, Stefania Magri, Mario Fichera, Anna Castaldo, Anna Nigri, Chiara Pinardi, Alessia Mongelli, Lidia Sarro, Davide Pareyson, Marina Grisoli, Cinzia Gellera, Daniela Di Bella, Caterina Mariotti, Franco Taroni
Summary: This study identified a form of spinocerebellar ataxia (SCA) characterized by the presence of an intermediate-length expansion in the TATA-box binding protein gene (TBP40-46) and a pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1), representing the first example of digenic inheritance in a cerebellar disorder. Patients with SCA(TBP/STUB1) exhibited multi-domain dementia and more severe impairment compared to those carrying only fully expanded SCA17 alleles. Neuroimaging analysis revealed reduced cerebellar volume and thickness in SCA(TBP/STUB1) patients, as well as basal ganglia volume reduction in both patient groups. The findings have implications for diagnosis and genetic counseling in families with hereditary and sporadic ataxia.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Anna Castaldo, Mariangela Farinotti, Mario Fichera, Lorenzo Nanetti, Filippo Fortuna, Caterina Mariotti, Alessandra Solari
Summary: This study translated and culturally adapted the PROM-Ataxia questionnaire into Italian and conducted cognitive interviews. Italian patients found the questionnaire to be complete, but identified some redundant or ambiguous items. The translation and cultural adaptation are necessary for the subsequent psychometric validation of the scale.
NEUROLOGICAL SCIENCES
(2023)
Article
Neurosciences
Jenny Lange, Olivia Gillham, Michael Flower, Heather Ging, Simon Eaton, Sneha Kapadia, Andreas Neueder, Michael R. Duchen, Patrizia Ferretti, Sarah J. Tabrizi
Summary: Huntington's Disease is a neurodegenerative disease caused by a genetic mutation. Astrocyte dysfunction, specifically changes in gene expression and metabolic activity, plays a role in the pathogenesis of the disease. Additionally, all Huntington's Disease astrocytes exhibit increased DNA damage and a DNA damage response, suggesting a potential mechanism for their dysfunction.
PROGRESS IN NEUROBIOLOGY
(2023)
Editorial Material
Neurosciences
Mena Farag, Desiree M. Salanio, Cara Hearst, Daniela Rae, Sarah J. Tabrizi
Summary: Advance care planning (ACP) is a beneficial tool that allows adult patients to express and formalize their beliefs, preferences, and wishes regarding future medical care. For Huntington's disease (HD) patients, early consideration of ACP is crucial due to challenges in determining decision-making capacity in the later stages of the disease. ACP empowers patients and provides reassurance to clinicians and surrogate decision makers by ensuring that medical management aligns with the patient's expressed wishes. Regular follow-up is necessary to maintain consistency in decisions and wishes. We outline the framework of our dedicated ACP clinic within the HD service, emphasizing the importance of patient-centered and personalized care plans that reflect the patient's goals, preferences, and values.
JOURNAL OF HUNTINGTONS DISEASE
(2023)
Article
Clinical Neurology
Andreas-Antonios Roussakis, Marta Gennaro, Mark Forrest Gordon, Ralf Reilmann, Beth Borowsky, Gail Rynkowski, Nicholas P. Lao-Kaim, Zoe Papoutsou, Juha-Matti Savola, Michael R. Hayden, David R. Owen, Nicola Kalk, Anne Lingford-Hughes, Roger N. Gunn, Graham Searle, Sarah J. Tabrizi, Paola Piccini
Summary: This longitudinal study demonstrates that the treatment of laquinimod in Huntington's disease does not affect regional microglia activation. Microglia activation is believed to be related to inflammation in the central nervous system and the progression of Huntington's disease. However, laquinimod is capable of regulating microglia. The study also shows that C-11-PBR28 PET-CT imaging can be used to assess regional gliosis and the effects of laquinimod treatment.
BRAIN COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Sangeerthana Rajagopal, Jasmine Donaldson, Michael Flower, Davina J. Hensman Moss, Sarah J. Tabrizi
Summary: Repeat expansion disorders (REDs) are monogenic diseases caused by repetitive DNA sequences expanding beyond a pathogenic threshold. The length of the repeat sequence is a major determinant of age at onset and disease progression. Phenotypic variability in REDs is influenced by factors such as the gene involved, the location of the repeat sequence, and the presence of interruptions. DNA repair pathways have been identified as potential modifiers of RED phenotypes, offering potential targets for disease-modifying therapies.
EMERGING TOPICS IN LIFE SCIENCES
(2023)
Article
Clinical Neurology
Nir Giladi, Roy N. Alcalay, Gary Cutter, Thomas Gasser, Tanya Gurevich, Guenter U. Hoeglinger, Kenneth Marek, Claudio Pacchetti, Anthony H. Schapira, Clemens R. Scherzer, Tanya Simuni, Pascal Minini, S. Pablo Sardi, M. Judith Peterschmitt
Summary: The safety, efficacy, and target engagement of venglustat in early-stage Parkinson's disease patients with GBA1 variants were assessed. The study showed that venglustat had a satisfactory safety profile but did not show beneficial treatment effect compared with placebo. These findings suggest that glucosylceramide synthase inhibition with venglustat may not be a viable therapeutic approach for GBA1-associated Parkinson's disease.
Letter
Clinical Neurology
Christos Koros, Kathrin Brockmann, Athina-Maria Simitsi, Anastasia Bougea, Hui Liu, Ann-Kathrin Hauser, Claudia Schulte, Stefanie Lerche, Ioanna Pachi, Nikolaos Papagiannakis, Roubina Antonelou, Athina Zahou, Isabel Wurster, Efthymia Efthymiopoulou, Ion Beratis, Matina Maniati, Marina Moraitou, Helen Michelakakis, Georgios Paraskevas, Sokratis G. Papageorgiou, Constantin Potagas, Dimitra Papadimitriou, Maria Bozi, Maria Stamelou, Thomas Gasser, Leonidas Stefanis
MOVEMENT DISORDERS
(2023)