Article
Genetics & Heredity
Karolina Pierzynowska, Magdalena Podlacha, Dorota Luszczek, Estera Rintz, Lidia Gaffke, Zuzanna Szczudlo, Marta Tomczyk, Ryszard T. Smolenski, Grzegorz Wegrzyn
Summary: This study identified abnormal hair morphology as a potential simple marker for testing therapeutic effects or disease progression in widely used HD mouse models R6/1 and R6/2.
Article
Biochemistry & Molecular Biology
Roberto Speziale, Camilla Montesano, Giulia Di Pietro, Daniel Oscar Cicero, Vincenzo Summa, Edith Monteagudo, Laura Orsatti
Summary: Huntington's disease (HD) is a genetic condition caused by the expansion of a specific sequence in the huntingtin gene. There is a lack of effective treatments for HD, highlighting the need for reliable mouse models for preclinical studies. This study utilized a urinary liquid chromatography-high-resolution mass spectrometry analysis to identify metabolic changes in different HD mouse models, aiming to improve our understanding of the disease and identify potential biomarkers.
Article
Neurosciences
Estibaliz Etxeberria-Rekalde, Saioa Alzola-Aldamizetxebarria, Stefanie Flunkert, Isabella Hable, Magdalena Daurer, Joerg Neddens, Birgit Hutter-Paier
Summary: Researchers conducted a comprehensive analysis of R6/2 mice, identifying Ctip2 and TSPO as new markers associated with the motor system and early neuroinflammation, providing a new direction for the study of HD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
S. M. Holley, K. D. Oikonomou, C. M. Swift, L. Mohan, B. Matthews, O. Vega, G. Mkrtchyan, C. Cepeda, M. S. Levine
Summary: As Huntington's disease progresses, there is a loss of neurons in the striatum and thinning of the cerebral cortex. This study found reduced connectivity between thalamic cells and their targeted cortical regions in a mouse model of HD, suggesting impaired thalamocortical information transmission.
Article
Multidisciplinary Sciences
Marie Katrin Bondulich, Yilan Fan, Yeojin Song, Flaviano Giorgini, Gillian P. Bates
Summary: KMO depletion in HD mice can normalize dysregulated KP genes in peripheral tissues and increase levels of neuroprotective metabolites, but it does not improve behavioral phenotypes. Peripheral inflammation levels, including pro-inflammatory cytokines, are modulated by KMO deletion, suggesting a potential role in HD pathogenesis.
SCIENTIFIC REPORTS
(2021)
Article
Ophthalmology
Yixuan Yao, Yujuan Cai, Ailing Sui, Yiyun Yao, Ting Su, Yanji Zhu, Bing Xie, Xi Shen
Summary: Through in vivo and in vitro experiments, it was found that etanercept regulates the expression of pro/anti-inflammatory factors, reduces the expression of pro-angiogenic factors, and decreases RNV formation by inhibiting NF-κB phosphorylation.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Masayo Hashimoto, Kenichi Watanabe, Kan Miyoshi, Yukako Koyanagi, Jun Tadano, Izuru Miyawaki
Summary: The study in the R6/2 mouse model revealed disturbances in histidine metabolism in brain tissue, as well as differential metabolites related to arginine and cysteine metabolism. Additionally, dysregulation of lipid metabolism was identified, indicating a wide range of metabolic alterations in the brain of R6/2 mice.
Article
Allergy
Cui-Cui Tian, Xue-Chen Ai, Jian-Chi Ma, Feng-Qiu Hu, Xiu-Ting Liu, Yi-Jin Luo, Guo-Zhen Tan, Jun -Min Zhang, Xi-Qing Li, Qing Guo, Fan-Qin Zeng, Zhen-Rui Shi, Liangchun Wang
Summary: This study compared the efficacy and safety of IVIG and systemic steroids with or without the tumor necrosis factor-a inhibitor etanercept in the treatment of SJS/TEN patients. The results showed that adding etanercept significantly reduced the duration of hospitalization, exposure time to high-dose steroids, and the overall amount of systemic steroids compared to conventional therapy, without pronounced adverse effects.
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
(2022)
Article
Neurosciences
Julien Gasser, Gaelle Gillet, Jorge S. Valadas, Laura Rouviere, Apoorva Kotian, Wenqiang Fan, James Keaney, Irena Kadiu
Summary: This study found that Huntington's disease leads to brain infiltration of peripheral lymphoid and myeloid cells, resulting in activation of microglia and enhanced phagocytic functions, which in turn contribute to synaptic loss. Similar observations were made in human Huntington's disease brains. Overall, targeting microglial functions related to synaptic surveillance and pruning may have therapeutic benefits in attenuating cognitive decline and psychiatric symptoms of Huntington's disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Nan Yan, Shuai Wang, Haotian Gao, Jiaqi Chen, Jiahui Cao, Pengsheng Wei, Xue Li, Ying Yu, Yan Wang, Yalin Niu, Yijie Wang, Shuyuan Liu, Ge Jin
Summary: Aloe emodin, derived from aloe or rhubarb, has various therapeutic effects including anti-renal fibrosis, anti-atherosclerosis, anti-cancer, and neuroprotective effects in ischemic stroke. In this study, aloe emodin was found to improve motor coordination and attenuate visual recognition impairment in HD R6/1 transgenic mice. It achieved this by inhibiting the phosphorylation of CaMKII and TGF-beta 1/Smad signaling, downregulating mutant huntingtin protein levels, and inhibiting neuronal apoptosis. These findings suggest that aloe emodin may be a potential therapeutic option for HD.
Article
Neurosciences
Katerina D. Oikonomou, Elissa J. Donzis, Minh T. N. Bui, Carlos Cepeda, Michael S. Levine
Summary: The study using the R6/2 mouse model found that the amplitude of somatic calcium transients in CPNs of Huntington's disease patients was reduced, but compensated by increased decay times, so that transient areas were similar between genotypes. Ryanodine receptors (RyRs) and L-type calcium channels may be potential targets for therapeutic intervention.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Richard J. Mills, Sean J. Humphrey, Patrick R. J. Fortuna, Mary Lor, Simon R. Foster, Gregory A. Quaife-Ryan, Rebecca L. Johnston, Troy Dumenil, Cameron Bishop, Rajeev Rudraraju, Daniel J. Rawle, Thuy Le, Wei Zhao, Leo Lee, Charley Mackenzie-Kludas, Neda R. Mehdiabadi, Christopher Halliday, Dean Gilham, Li Fu, Stephen J. Nicholls, Jan Johansson, Michael Sweeney, Norman C. W. Wong, Ewelina Kulikowski, Kamil A. Sokolowski, Brian W. C. Tse, Lynn Devilee, Holly K. Voges, Liam T. Reynolds, Sophie Krumeich, Ellen Mathieson, Dad Abu-Bonsrah, Kathy Karavendzas, Brendan Griffen, Drew Titmarsh, David A. Elliott, James McMahon, Andreas Suhrbier, Kanta Subbarao, Enzo R. Porrello, Mark J. Smyth, Christian R. Engwerda, Kelli P. A. MacDonald, Tobias Bald, David E. James, James E. Hudson
Summary: Cardiac injury and dysfunction in COVID-19 patients increase mortality risk. An inflammatory cytokine-storm can induce diastolic dysfunction, but BET inhibitors show promise in preventing cardiac damage and dysfunction induced by the virus.
Article
Food Science & Technology
Jong Yeon Park, Bich Hang Do, Ju-Seung Lee, Hyun Cheol Yang, Anh Ngoc Nguyen, Martin Krupa, Chong Jai Kim, Yeon Jin Jang, Han Choe
Summary: The study found that recombinant crotamine has significant antinociceptive and anti-inflammatory effects, which are not related to the opioid receptor. Additionally, the effects of intraperitoneal or intraplantar recombinant crotamine are related to TNF-alpha.
Editorial Material
Hematology
Federico Simonetta
Summary: The study demonstrates that dual blockade of TNF-α and IL-6R provides a significant advantage over single-cytokine blockade in protecting mice from lethal graft-versus-host disease.
Article
Immunology
Caterina Defendenti, Maciej Tarkowski, Simona Borille, Andrea Cassinotti, Alessandro Massari, Sarah Birindelli, Agostino Riva, Sandro Ardizzone, Mauro Panteghini
Summary: In patients with IBD, the frequency of peripheral blood CD70+ T cells was significantly reduced by treatment with anti-TNF alpha antibodies, indicating a 'cooling' effect of the biological therapy. However, CD19+27+ memory B cells did not show significant differences between groups. Monitoring of these lymphocyte subtypes may provide better insight into disease progression and therapy application in IBD patients.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Clinical Neurology
Joaquim J. Ferreira, Filipe B. Rodrigues, Goncalo S. Duarte, Tiago A. Mestre, Anne-Catherine Bachoud-Levi, Anna Rita Bentivoglio, Jean-Marc Burgunder, Francisco Cardoso, Daniel O. Claassen, G. Bernard Landwehrmeyer, Jaime Kulisevsky, Melissa J. Nirenberg, Anne Rosser, Jan Roth, Klaus Seppi, Jaroslaw Slawek, Erin Furr-Stimming, Sarah J. Tabrizi, Francis O. Walker, Wim Vandenberghe, Joao Costa, Cristina Sampaio
Summary: The management of Huntington's disease (HD) is challenging and mainly consists of off-label treatments. A task force was commissioned to review available therapies for HD gene expansion carriers. Limited data supports the use of VMAT2 inhibitors for specific motor symptoms.
MOVEMENT DISORDERS
(2022)
Article
Psychology, Clinical
Akshay Nair, Ritwik K. Niyogi, Fei Shang, Sarah J. Tabrizi, Geraint Rees, Robb B. Rutledge
Summary: This study provides new insights into understanding and explaining apathy, a disabling neuropsychiatric symptom, by investigating the relationship between the opportunity cost of time (OCT), self-initiation, and apathy. The findings suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Neuroimaging
Paul Zeun, Peter McColgan, Thijs Dhollander, Sarah Gregory, Eileanoir B. Johnson, Marina Papoutsi, Akshay Nair, Rachael Scahill, Geraint Rees, Sarah J. Tabrizi
Summary: The study found that cortico-basal ganglia white matter loss begins in premanifest Huntington's disease (preHD) approximately 11 years before symptom onset. The most vulnerable white matter tracts are those connecting the striatum and thalamus. Additionally, there is a significant correlation between fiber density and cross section in these tracts and the Unified Huntington's disease rating scale (UHDRS) total motor score (TMS).
NEUROIMAGE-CLINICAL
(2022)
Letter
Clinical Neurology
Ramita Dewan, Zane Jaunmuktane, Monica Emili Garcia-Segura, Catherine Strand, Edward Wild, Joaquin Villar, Clifton L. Dalgard, Sarah J. Tabrizi, Bryan J. Traynor, Christos Proukakis
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Carlos Estevez-Fraga, Filipe B. Rodrigues, Sarah J. Tabrizi, Edward J. Wild
Summary: This edition of the Huntington's Disease Clinical Trials Corner provides detailed information on the GENERATION HD1, PRECISION-HD1 and PRECISION-HD2, SELECT-HD, and VIBRANT-HD trials, as well as a list of all currently registered and ongoing clinical trials in Huntington's disease.
JOURNAL OF HUNTINGTONS DISEASE
(2022)
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
Chin-Fu Liu, Laurent Younes, Xiao J. Tong, Jared T. Hinkle, Maggie Wang, Sanika Phatak, Xin Xu, Xuan Bu, Vivian Looi, Jee Bang, Sarah J. Tabrizi, Rachael Scahill, Jane S. Paulsen, Nellie Georgiou-Karistianis, Andreia Faria, Michael Miller, J. Tilak Ratnanather, Christopher A. Ross
Summary: Huntington's disease is caused by a CAG repeat expansion in the Huntingtin gene, resulting in increased polyglutamine in the Huntingtin protein. This study analyzed three longitudinal datasets and found significant selective atrophy in multiple regions, supporting the hypothesis of circuit-based spread of pathology in Huntington's disease.
BRAIN COMMUNICATIONS
(2023)
Meeting Abstract
Clinical Neurology
Lauren M. Byrne, Jordan L. Schultz, Sophie Field, Kate Fayer, Yara Hassan, Filipe B. Rodrigues, Ellen van der Plas, Douglas Langbehn, Sarah J. Tabrizi, Peggy C. Nopoulos, Edward J. Wild
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Annabelle Coleman, Mackenzie T. Langan, Gaurav Verma, Harry Knights, Rachelle Dar Santos, Allison Coleman, Aaron Sturrock, Blair R. Leavitt, Sarah J. Tabrizi, Rachael I. Scahill, Nicola Z. Hobbs
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Jasmine Donaldson, Joseph Hamilton, Jessica Olive, Robert Goold, Sarah J. Tabrizi
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Ross Ferguson, Michael Flower, Sarah J. Tabrizi
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Sophie Field, Alexandra Durr, Raymund Ac Roos, Blair Leavitt, Sarah J. Tabrizi, Rachael I. Scahill
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)