Article
Multidisciplinary Sciences
Igor Koval, Thomas Dighiero-Brecht, Allan J. Tobin, Sarah J. Tabrizi, Rachael Scahill, Sophie Tezenas du Montcel, Stanley Durrleman, Alexandra Durr
Summary: This study utilizes disease course mapping to forecast biomarker progression for individual carriers of the pathological CAG repeat expansions responsible for Huntington disease, in order to select participants at risk for progression and compute the power of trials for such an enriched population, ultimately reducing sample sizes and ensuring a more homogeneous group of participants.
SCIENTIFIC REPORTS
(2022)
Article
Health Care Sciences & Services
Sabrina Maffi, Eugenia Scaricamazza, Simone Migliore, Melissa Casella, Consuelo Ceccarelli, Ferdinando Squitieri
Summary: This study investigated the correlations between sleep features and motor, cognitive, behavioral, and functional changes in individuals with Huntington's disease (HD). The results showed a significant association between sleep abnormalities and the severity of disease progression, as well as impaired independence, cognitive performance, and motor functions. Sleep abnormalities are an important aspect of the clinical profile of HD and can greatly impact patients' quality of life.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Orthopedics
Alvaro Reyes, Danielle M. Bartlett, Timothy J. Rankin, Pauline Zaenker, Kate Turner, Wei-Peng Teo, Shih Ching Fu, Josefa Domingos, Nellie Georgiou-Karistianis, Mel Ziman, Travis M. Cruickshank
Summary: Dual-tasking deficiencies are common in people with premanifest Huntington disease and may be influenced by poor sleep quality. Measures of dual-tasking show acceptable test-retest reliability in this population and should be considered when managing dual-tasking problems.
Review
Gastroenterology & Hepatology
Paul Y. Kwo, Tushar Patel
Summary: Clinical trials are crucial for advancing new therapies for liver diseases and adapting to emerging capabilities and external forces. The COVID-19 pandemic has prompted changes in clinical trial operations and opportunities for innovation in hepatology trials. Technological advances will drive future trials, incorporating digital capabilities and expanded data collection, computing, and analytics. Innovative trial designs and broader participant engagement will shape trial conduct, along with evolving regulatory needs and new stakeholders. The evolution of clinical trials presents unique opportunities to improve the lives of patients with liver diseases.
Review
Medicine, Research & Experimental
Shreya Asher, Ronny Priefer
Summary: This article reviews the history of clinical trials for Alzheimer's disease and analyzes the reasons for their failures.
Article
Clinical Neurology
Beate Schumann-Werner, Imis Dogan, Shahram Mirzazade, Bettina Mall, Rena Overbeck, Philipp Honrath, Jorg B. Schulz, Kathrin Reetz, Cornelius J. Werner
Summary: This study provides a comprehensive investigation of dysphagia in Huntington disease, revealing a communication disorder between sensory and motor networks involved in swallowing. The study also emphasizes the importance of early instrumental swallowing evaluation.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Psychology, Multidisciplinary
Shuhei Shiino, Nelleke Corine van Wouwe, Scott A. A. Wylie, Daniel O. O. Claassen, Katherine E. E. McDonell
Summary: This study investigated the temporal dynamics of action impulse control in Huntington disease (HD) patients using an inhibitory action control task. The results showed that HD patients had slower and less accurate reactions, as well as an exacerbated interference effect. However, they still preserved the ability to suppress impulsivity.
FRONTIERS IN PSYCHOLOGY
(2023)
Article
Pediatrics
Stephanie M. Cho, Stylianos Serghiou, John Pa Ioannidis, Terry P. Klassen, Despina G. Contopoulos-Ioannidis
Summary: The study found that a small proportion of large pediatric RCTs had industry funding, with most participants coming from lower-middle-income countries. Few trials targeted mortality as an outcome, and a significant number of trials completed for over 12 months remained unpublished. The number of trials correlated well with pediatric GBD, highlighting the importance of incentive collaborations, timely publication, and alignment with pediatric GBD for improving child health globally.
Editorial Material
Gastroenterology & Hepatology
Nurulamin M. Noor, Miles Parkes, Tim Raine
Summary: Recruitment rates in inflammatory bowel disease (IBD) trials are declining, prompting calls for modifications to make trials more efficient and patient-centered.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Review
Clinical Neurology
Hannah S. Bakels, Raymund A. C. Roos, Willeke M. C. van Roon-Mom, Susanne T. de Bot
Summary: Juvenile-onset Huntington disease is a rare form of the autosomal dominant brain disorder, accounting for approximately 5% of patients. It is characterized by distinct symptoms and signs, as well as more severe pathology of brain structures compared to adult-onset disease. Understanding the pathophysiological differences between juvenile- and adult-onset Huntington disease is crucial for developing new therapeutic strategies.
MOVEMENT DISORDERS
(2022)
Review
Biochemistry & Molecular Biology
Annalisa Tassone, Maria Meringolo, Giulia Ponterio, Paola Bonsi, Tommaso Schirinzi, Giuseppina Martella
Summary: Strong evidence suggests that the decline in mitochondrial function is correlated with degenerative diseases. Various types of neurodegenerative diseases, such as Huntington's chorea and Parkinson's disease, share mitochondrial bioenergy dysregulation as a common feature. These diseases have different manifestations and genetic factors, but they both involve neuronal dysfunction and striatal impairment. This review focuses on describing the onset and development of both diseases in relation to mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Faiez Zannad, Cynthia Chauhan, Patrick O. Gee, Nick Hartshorne-Evans, Adrian F. Hernandez, Marilyn K. Mann, Robin Martinez, Roxana Mehran
Summary: Patients are crucial end-users in medical therapies and should be actively involved as contributors and decision-makers throughout the product development process. While there is increasing recognition of this, cardiovascular research lags behind in terms of patient involvement and awareness of clinical trials in the field.
EUROPEAN HEART JOURNAL
(2022)
Article
Medicine, General & Internal
Gerardo Alfonso Perez, Javier Caballero Villarraso
Summary: This paper presents an approach to identify Huntington Disease patients using DNA CpG methylation data and non-linear techniques. By selecting specific CpG sites and employing methods like artificial neural networks, the approach accurately distinguishes between control and HD patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Amy Corneli, Emily Hanlen-Rosado, Kevin McKenna, Richardae Araojo, Dawn Corbett, Kaveeta Vasisht, Bernadette Siddiqi, Tesheia Johnson, Luther T. Clark, Sara B. Calvert
Summary: Women and racial/ethnic groups have been underrepresented in clinical trials in the US, leading to incomplete understanding of new medical products' safety and efficacy, as well as limited generalizability of trial findings. Inequities in outcomes and disparities may persist or worsen. Organizational-level approaches are needed to improve diversity and inclusion in clinical trials, with a focus on commitment, partnerships, accountability, and resources.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Gastroenterology & Hepatology
Emily C. L. Wong, Parambir S. Dulai, John K. Marshall, Vipul Jairath, Walter Reinisch, Neeraj Narula
Summary: Disease duration of less than 5 years is associated with clinical remission at the end of induction in Crohn's disease patients. Strategies to reduce placebo response rates in clinical trials should consider stratification or exclusion based on disease duration and mild disease severity as measured by objective biomarkers.
INFLAMMATORY BOWEL DISEASES
(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)
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
Clinical Neurology
Peter McColgan, Sarah Gregory, Paul Zeun, Angeliki Zarkali, Eileanoir B. Johnson, Christopher Parker, Kate Fayer, Jessica Lowe, Akshay Nair, Carlos Estevez-Fraga, Marina Papoutsi, Hui Zhang, Rachael Scahill, Sarah J. Tabrizi, Geraint Rees
Summary: McColgan et al. found that premanifest Huntington's disease gene carriers around 20 years from disease onset exhibit increased functional connectivity, which is correlated with elevated CSF neurofilament light. These changes occur in brain regions associated with gene expression specific to neuronal GABAergic and glutamatergic cells.
Article
Clinical Neurology
Sarah J. Tabrizi, Carlos Estevez-Fraga, Willeke M. C. van Roon-Mom, Michael D. Flower, Rachael I. Scahill, Edward J. Wild, Ignacio Munoz-Sanjuan, Cristina Sampaio, Anne E. Rosser, Blair R. Leavitt
Summary: Huntington's disease is a prevalent neurodegenerative disorder with complex molecular pathogenesis. Currently, there is no effective treatment available. Potential interventions include targeting huntingtin DNA and RNA, clearing huntingtin protein, and DNA repair pathways. Evaluating past trials and considering the current situation will help in addressing the challenges and opportunities for the future.
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
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)
Meeting Abstract
Clinical Neurology
Robert Goold, Joseph Hamilton, Thomas Menneteau, Michael Flower, Emma Bunting, Sarah Aldous, Antonio Porro, Jose Vicente, Nicholas Allen, Hilary Wilkinson, Gillian Bates, Alessandro Sartori, Konstantinos Thalassinos, Gabriel Balmus, Sarah Tabrizi
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Harry D. J. Knights, Annabelle Coleman, Nicola Z. Hobbs, Sarah J. Tabrizi, Rachael I. Scahill
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)