Article
Medicine, General & Internal
Klaudia Plinta, Andrzej Plewka, Magdalena Wojcik-Pedziwiatr, Nikola Zmarzly, Marcin Rudzinski, Monika Rudzinska-Bar
Summary: This study evaluated the use of plasma TGF-beta 1 levels in assessing Huntington's disease severity, and found that it is not suitable as a marker of the disease.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Clinical Neurology
Danielle A. Buchanan, Amy E. Brown, Elicia C. Osigwe, Anna C. Pfalzer, Leah G. Mann, Yan Yan, Hakmook Kang, Daniel O. Claassen
Summary: By analyzing the Enroll-HD longitudinal observational study, it was found that there are differences in the presentation and progression of Huntington's disease (HD) across race groups, with black participants being more severe at baseline. The factors driving clinical differences for black participants were considered, and the importance of improving the recruitment of Asian and black patients in rare disease studies was emphasized.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Pubu M. Abeyasinghe, Jeffrey D. Long, Adeel Razi, Dorian Pustina, Jane S. Paulsen, Sarah J. Tabrizi, Govinda R. Poudel, Nellie Georgiou-Karistianis
Summary: Potential therapeutic targets and clinical trials for Huntington's disease have expanded significantly in the last decade. This study aimed to distinguish longitudinal trajectories across different progression groups of Huntington's disease by combining clinical and morphometric imaging data. Putamen and caudate volumes were identified as key variables for differentiation and tracking disease progression within different groups. Monitoring volumetric changes alongside clinical end points may offer a more comprehensive understanding of functional outcomes and help refine the design of clinical trials.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Valter Niemela, Anne-Marie Landtblom, Dag Nyholm, Maria Kneider, Radu Constantinescu, Martin Paucar, Per Svenningsson, Sandy Abujrais, Joachim Burman, Ganna Shevchenko, Jonas Bergquist, Jimmy Sundblom
Summary: Identifying molecular changes in Huntington's disease is crucial for therapy development. Mass-spectrometry analysis revealed differences in protein expression between HD patients and controls, with PENK levels potentially serving as a marker for the state of medium spiny neurons in HD.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Ewa Modrzejewska-Zielonka, Michal Ren, Andrzej Mlodak, Jerzy Tadeusz Marcinkowski, Daniel Zielonka
Summary: This study aims to assess the burden of caregivers of Huntington's disease patients and identify biological and clinical factors related to the burden. The results show that caregivers were mostly burdened by patients' dependence and the discrepancy between reality and expectations. This study reveals factors that should be addressed to reduce caregivers' burden.
EUROPEAN NEUROLOGY
(2022)
Article
Clinical Neurology
Carlos Estevez-Fraga, Rachael Scahill, Alexandra Durr, Blair R. Leavitt, Raymund A. C. Roos, Douglas R. Langbehn, Geraint Rees, Sarah Gregory, Sarah J. Tabrizi
Summary: The composite Unified Huntington's Disease Rating Scale (cUHDRS) is correlated with imaging biomarkers and tracks atrophy progression in HD, supporting its biological relevance.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Hongshuai Liu, Chuangchuang Zhang, Jiadi Xu, Jing Jin, Liam Cheng, Xinyuan Miao, Qian Wu, Zhiliang Wei, Peiying Liu, Hanzhang Lu, Peter C. M. van Zijl, Christopher A. Ross, Jun Hua, Wenzhen Duan
Summary: Huntington's disease is a fatal neurodegenerative disorder caused by a mutation in the HTT gene, and research using a mouse model has shown that changes in CBVa can be detected in the premanifest stage of the disease, with non-allele-specific HTT silencing showing promising therapeutic effects.
Review
Neurosciences
Joshua Barry, Allison Peng, Michael S. Levine, Carlos Cepeda
Summary: Huntington's disease is a fatal neurodegenerative disorder that affects striatal and cortical neurons, leading to synapse loss and cell death. Perturbed calcium (Ca2+) homeostasis plays a crucial role in the disease, and imaging techniques can monitor neuronal activity and Ca2+ dynamics.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Clinical Neurology
Amrita Mohan, Zhaonan Sun, Soumya Ghosh, Ying Li, Swati Sathe, Jianying Hu, Cristina Sampaio
Summary: A study developed and validated a model of Huntington's disease progression using machine-learning methods, identifying nine disease states and revealing transition probabilities ranging from 5% to 27%. The findings can improve trial design and participant selection.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Naghmeh Ghazaleh, Richard Houghton, Giuseppe Palermo, Scott A. Schobel, Peter A. Wijeratne, Jeffrey D. Long
Summary: This study investigated potential prognostic variables in patients with Huntington's disease (HD) using the Enroll-HD cohort and trained a random forest regression model to predict clinical outcomes. Novel predictors such as being accompanied at clinical visit and cognitive impairment, in addition to established predictors like CAG repeat length, were found to improve the model's ability to predict clinical outcomes. These novel prognostic variables may be considered for statistical control in HD clinical studies.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Yunping Deng, Hongbing Wang, Marion Joni, Radhika Sekhri, Anton Reiner
Summary: Using behavioral testing and morphological methods, we found that in male heterozygous Q175 mice, striatal neuron abnormalities and behavioral deficits begin to develop between 2 and 6 months of age, reflecting early effects of the HD mutation. While no significant loss of striatal neurons was observed at 18 months, there were signs of reduced expression and dendrite attenuation in certain neuron types as early as 6 months. Additionally, certain types of neurons, such as FoxP2+ arkypallidal GPe neurons and subthalamic nucleus neurons, were lost by 18 months but others, like prototypical PARV+ GPe neurons or dopaminergic nigral neurons, remained unaffected.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marian Merino, Sonia Gonzalez, Ma Carmen Tronch, Ana Virginia Sanchez-Sanchez, Ma Paz Clares, Antonio Garcia-Espana, Enrique Garcia-Espana, Jose L. Mullor
Summary: Huntington's disease is a rare inherited neurodegenerative disorder with no cure. A small molecule called 4QMn has shown potential to improve the disease phenotype in mice, suggesting it could be a therapeutic option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Seung Ho Choi, KyoungJoo Cho
Summary: The study demonstrated that let7b miRNA can increase LAMP2A and reduce extended polyQ in mouse striatal cells. The level of let7b was highly expressed in the striatum of pre-onset HD mice, but significantly reduced in post-onset HD mice. These findings suggest that LAMP2A related to chaperone-mediated autophagy (CMA) capacity may play a crucial role in the onset and progression of HD symptoms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Tripti Joshi, Vipendra Kumar, Elena V. Kaznacheyeva, Nihar Ranjan Jana
Summary: Withaferin A, a bioactive molecule derived from an Indian medicinal plant, shows potential in rescuing defective proteostasis and delaying disease progression in Huntington's disease (HD). By activating heat shock response and reducing mutant huntingtin aggregation, Withaferin A treatment improves motor deficits and increases lifespan in HD mice models. This compound also decreases inflammatory processes and has potential for treating neurodegenerative disorders involving protein misfolding and aggregation.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Aynur Soenmez, Rasem Mustafa, Salome T. Ryll, Francesca Tuorto, Ludivine Wacheul, Donatella Ponti, Christian Litke, Tanja Hering, Kerstin Kojer, Jenniver Koch, Claudia Pitzer, Joachim Kirsch, Andreas Neueder, Grzegorz Kreiner, Denis L. J. Lafontaine, Michael Orth, Birgit Liss, Rosanna Parlato
Summary: Transcriptional and cellular-stress surveillance deficits are characteristic features of Huntington's disease (HD), caused by pathological expansion of CAG repeats. Nucleolar dysfunction impacts HD pathophysiology, with genetic disruption decreasing mHTT distribution in vulnerable neurons and exacerbating motor deficits. NPM1 delocalization is identified as a novel histopathological marker of HD progression.
CELL DEATH & DISEASE
(2021)