15 results on '"Gonzalez‐Robles, Cristina"'
Search Results
2. Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.
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Zeissler, Marie-Louise, Bakshi, Nikul, Bartlett, Michèle, Batla, Amit, Byrom, David, Chapman, Rebecca, Collins, Sally, Cowd, Elaine, Deeson, Eric, Ellis-Doyle, Romy, Forbes, Jodie, Gonzalez-Robles, Cristina, Jewell, Anna, Lane, Emma L., LaPelle, Nancy R., Martin, Keith, Matthews, Helen, Miller, Laurel, Mills, Georgia, and Morgan, Antony
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PARKINSON'S disease ,PATIENT participation ,CLINICAL trials ,CONSORTIA ,MOVEMENT disorders ,SEMI-structured interviews - Abstract
Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD. Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project. Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors. Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review – identifying impact of PPIE on project outputs. Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Elevated Bile Acid 3β,5α,6β-Trihydroxycholanoyl Glycine in a Subset of Adult Ataxias Including Niemann–Pick Type C.
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Motamed-Gorji, Nazgol, Khalil, Youssef, Gonzalez-Robles, Cristina, Khan, Shamsher, Mills, Philippa, Garcia-Moreno, Hector, Ging, Heather, Tariq, Ambreen, Clayton, Peter T., and Giunti, Paola
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BILE acids ,FRIEDREICH'S ataxia ,FARNESOID X receptor ,WHOLE genome sequencing ,GLYCINE ,ADULTS - Abstract
Ataxia is a common neurological feature of Niemann–Pick disease type C (NPC). In this disease, unesterified cholesterol accumulates in lysosomes of the central nervous system and hepatic cells. Oxidation by reactive oxygen species produces oxysterols that can be metabolised to specific bile acids. These bile acids have been suggested as useful biomarkers to detect NPC. Concentrations of 3β,5α,6β-trihydroxycholanyl glycine (3β,5α,6β-triOH-Gly) and 3β,7β-dihydroxy-5-cholenyl glycine (3β,7β-diOH-Δ5-Gly) were measured in plasma of 184 adults with idiopathic ataxia. All patients were tested with whole genome sequencing containing hereditary ataxia panels, which include NPC1 and NPC2 mutations and other genetic causes of ataxia. Plasma 3β,5α,6β-triOH-Gly above normal (>90 nM) was found in 8 out of 184 patients. One patient was homozygous for the p.(Val1165Met) mutation in the NPC1 gene. The remaining seven included one patient with Friedreich's ataxia and three patients with autoimmune diseases. Oxidative stress is known to be increased in Friedreich's ataxia and in autoimmune diseases. Therefore, this subset of patients possibly shares a common mechanism that determines the increase of this bile acid. In a large cohort of adults with ataxia, plasma 3β,5α,6β-triOH-Gly was able to detect the one patient in the cohort with NPC1 disease, but also detected oxidation of cholesterol by ROS in other disorders. Plasma 3β,7β-diOH-Δ5-Gly is not a potential biomarker for NPC1. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Stage‐dependent biomarker changes in spinocerebellar ataxia type 3
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Faber, Jennifer, primary, Berger, Moritz, additional, Wilke, Carlo, additional, Hubener‐Schmid, Jeannette, additional, Schaprian, Tamara, additional, Santana, Magda M, additional, Grobe‐Einsler, Marcus, additional, Onder, Demet, additional, Koyak, Berkan, additional, Giunti, Paola, additional, Garcia‐Moreno, Hector, additional, Gonzalez‐Robles, Cristina, additional, Lima, Manuela, additional, Raposo, Mafalda, additional, Melo, Ana Rosa Vieira, additional, Pereira de Almeida, Luís, additional, Silva, Patrick, additional, Pinto, Maria M, additional, van de Warrenburg, Bart P., additional, van Gaalen, Judith, additional, de Vries, Jeroen, additional, Oz, Gulin, additional, Joers, James M., additional, Synofzik, Matthis, additional, Schols, Ludger, additional, Riess, Olaf, additional, Infante, Jon, additional, Manrique, Leire, additional, Timmann, Dagmar, additional, Thieme, Andreas, additional, Jacobi, Heike, additional, Reetz, Kathrin, additional, Dogan, Imis, additional, Onyike, Chiadikaobi, additional, Povazan, Michal, additional, Schmahmann, Jeremy, additional, Ratai, Eva‐Maria, additional, Schmid, Matthias, additional, and Klockgether, Thomas, additional
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- 2023
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5. Embedding Patient Input in Outcome Measures for Long‐Term Disease‐Modifying Parkinson Disease Trials.
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Gonzalez‐Robles, Cristina, Bartlett, Michèle, Burnell, Matthew, Clarke, Caroline S., Haar, Shlomi, Hu, Michele T., Huxford, Brook, Jha, Ashwani, Lawton, Michael, Noyce, Alastair, Piccini, Paola, Pushparatnam, Kuhan, Rochester, Lynn, Siu, Carroll, van Wamelen, Daniel, Williams‐Gray, Caroline H., Zeissler, Marie‐Louise, Zetterberg, Henrik, Carroll, Camille B., and Foltynie, Thomas
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Background: Clinical trials of disease‐modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. Objectives: The objective is to select a patient‐centered primary outcome measure for disease‐modification trials over three or more years. Methods: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. Results: Although initial considerations favored the Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS‐UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS‐UPDRS Parts I + II sum score. Conclusions: The MDS‐UPDRS Parts I + II sum score was chosen as the primary outcome for large 3‐year disease‐modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Stage‐Dependent Biomarker Changes in Spinocerebellar Ataxia Type 3.
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Faber, Jennifer, Berger, Moritz, Wilke, Carlo, Hubener‐Schmid, Jeannette, Schaprian, Tamara, Santana, Magda M., Grobe‐Einsler, Marcus, Onder, Demet, Koyak, Berkan, Giunti, Paola, Garcia‐Moreno, Hector, Gonzalez‐Robles, Cristina, Lima, Manuela, Raposo, Mafalda, Melo, Ana Rosa Vieira, de Almeida, Luís Pereira, Silva, Patrick, Pinto, Maria M., van de Warrenburg, Bart P., and van Gaalen, Judith
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CEREBELLUM degeneration ,SPINOCEREBELLAR ataxia ,BIOMARKERS ,WHITE matter (Nerve tissue) ,DISEASE vectors ,ATAXIA ,CYTOPLASMIC filaments - Abstract
Spinocerebellar ataxia type 3/Machado–Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross‐sectional data of 292 spinocerebellar ataxia type 3/Machado–Joseph disease mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whereas neurofilament light deviated from normal 13.3 years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2 years and 0.6 years before ataxia onset. We propose a staging model of spinocerebellar ataxia type 3/Machado–Joseph disease that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset. ANN NEUROL 2024;95:400–406 [ABSTRACT FROM AUTHOR]
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- 2024
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7. A standardised protocol for blood and cerebrospinal fluid collection and processing for biomarker research in ataxia
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Santana, Magda M., Gaspar, Laetitia S., Pinto, Maria M., Silva, Patrick, Adão, Diana, Pereira, Dina, Ribeiro, Joana Afonso, Cunha, Inês, Huebener-Schmid, Jeannette, Raposo, Mafalda, Ferreira, Ana F., Faber, Jennifer, Kuhs, Sandra, Garcia-Moreno, Hector, Reetz, Kathrin, Thieme, Andreas, Infante, Jon, Warrenburg, Bart P. C. van de, Giunti, Paola, Riess, Olaf, Schöls, Ludger, Lima, Manuela, Klockgether, Thomas, Januário, Cristina, Almeida, Luís Pereira de, Krahe, Janna, Gaalen, Judith van, Gonzalez-Robles, Cristina, Fleszar, Zofia, Pelayo-Negro, Ana Lara, Manrique, Leire, Timmann-Braun, Dagmar, Steiner, Katharina M., Melo, Ana Rosa Vieira, van de Warrenburg, Bart P. C., de Almeida, Luís Pereira, van Gaalen, Judith, Krahe, Janna, van Gaalen, Judith, Gonzalez-Robles, Cristina, Fleszar, Zofia, Pelayo-Negro, Ana Lara, Manrique, Leire, Timmann, Dagmar, Steiner, Katharina M, and Melo, Ana Rosa Vieira
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Histology ,research ,Cerebellar Ataxia ,ataxia ,Medizin ,biomarkers ,standardisation ,Machado-Joseph Disease ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,cerebrospinal fluid ,Pathology and Forensic Medicine ,All institutes and research themes of the Radboud University Medical Center ,Neurology ,blood ,Physiology (medical) ,Humans ,Spinocerebellar Ataxias ,neurodegenerative diseases ,Neurology (clinical) ,ddc:610 ,protocol ,Spinocerebellar Degenerations - Abstract
Contains fulltext : 292317.pdf (Publisher’s version ) (Open Access) The European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) is a consortium established with the ambition to set up the largest European longitudinal trial-ready cohort of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD), the most common autosomal dominantly inherited ataxia worldwide. A major focus of ESMI has been the identification of SCA3/MJD biomarkers to enable future interventional studies. As biosample collection and processing variables significantly impact the outcomes of biomarkers studies, biosampling procedures standardisation was done previously to study visit initiation. Here, we describe the ESMI consensus biosampling protocol, developed within the scope of ESMI, that ultimately might be translated to other neurodegenerative disorders, particularly ataxias, being the first step to protocol harmonisation in the field. 01 april 2023
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- 2023
8. Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative.
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Gonzalez-Robles, Cristina, Weil, Rimona S., van Wamelen, Daniel, Bartlett, Michèle, Burnell, Matthew, Clarke, Caroline S., Hu, Michele T., Huxford, Brook, Jha, Ashwani, Lambert, Christian, Lawton, Michael, Mills, Georgia, Noyce, Alastair, Piccini, Paola, Pushparatnam, Kuhan, Rochester, Lynn, Siu, Carroll, Williams-Gray, Caroline H., Zeissler, Marie-Louise, and Zetterberg, Henrik
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PARKINSON'S disease , *TRIALS (Law) , *QUALITY of life - Abstract
Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease
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Foltynie, Tom, Gandhi, Sonia, Gonzalez-Robles, Cristina, Zeissler, Marie-Louise, Mills, Georgia, Barker, Roger, Carpenter, James, Schrag, Anette, Schapira, Anthony, Bandmann, Oliver, Mullin, Stephen, Duffen, Joy, McFarthing, Kevin, Chataway, Jeremy, Parmar, Mahesh, Carroll, Camille, EJS ACT-PD Consortium, Foltynie, Tom [0000-0003-0752-1813], Schapira, Anthony [0000-0002-3018-3966], Bandmann, Oliver [0000-0001-6753-7847], Chataway, Jeremy [0000-0001-7286-6901], and Apollo - University of Cambridge Repository
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multi-stage ,complex innovative trial design ,platform trial ,Parkinson’s disease ,Humans ,COVID-19 ,Parkinson Disease ,multi-arm - Abstract
An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson's disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson's disease, a multi-arm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson's disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson's disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson's disease.
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- 2023
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10. 109 Embedding patient voice in trial design: the EJS ACT-PD experience
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Zeissler, Marie-Louise, primary, McFarthing, Kevin, additional, Gonzalez-Robles, Cristina, additional, Chapman, Rebecca, additional, Mills, Georgia, additional, Foltynie, Tom, additional, and Carroll, Camille, additional
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- 2022
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11. A Drug Combination Rescues Frataxin-Dependent Neural and Cardiac Pathophysiology in FA Models
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Abeti, Rosella, primary, Jasoliya, Mittal, additional, Al-Mahdawi, Sahar, additional, Pook, Mark, additional, Gonzalez-Robles, Cristina, additional, Hui, Chun Kiu, additional, Cortopassi, Gino, additional, and Giunti, Paola, additional
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- 2022
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12. From Collar to Coccyx: Truncal Movement Disorders: A Clinical Review
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Colucci, Fabiana, primary, Carvalho, Vanessa, additional, Gonzalez‐Robles, Cristina, additional, Bhatia, Kailash P., additional, and Mulroy, Eoin, additional
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- 2021
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13. Throat‐Clearing Vocalizations in Primary Brain Calcification Syndromes
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Mulroy, Eoin, primary, Ilinca, Andreea, additional, Gonzalez‐Robles, Cristina, additional, Magrinelli, Francesca, additional, Puschmann, Andreas, additional, and Bhatia, Kailash P., additional
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- 2021
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14. Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease.
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Foltynie T, Gandhi S, Gonzalez-Robles C, Zeissler ML, Mills G, Barker R, Carpenter J, Schrag A, Schapira A, Bandmann O, Mullin S, Duffen J, McFarthing K, Chataway J, Parmar M, and Carroll C
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- Humans, COVID-19, Parkinson Disease
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An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson's disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson's disease, a multi-arm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson's disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson's disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson's disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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15. Stage-dependent biomarker changes in spinocerebellar ataxia type 3.
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Faber J, Berger M, Carlo W, Hübener-Schmid J, Schaprian T, Santana MM, Grobe-Einsler M, Onder D, Koyak B, Giunti P, Garcia-Moreno H, Gonzalez-Robles C, Lima M, Raposo M, Melo ARV, de Almeida LP, Silva P, Pinto MM, van de Warrenburg BP, van Gaalen J, de Vries J, Jeroen, Oz G, Joers JM, Synofzik M, Schöls L, Riess O, Infante J, Manrique L, Timmann D, Thieme A, Jacobi H, Reetz K, Dogan I, Onyike C, Povazan M, Schmahmann J, Ratai EM, Schmid M, and Klockgether T
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Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI. Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage defined by absence of ataxia, but a significant rise of NfL. The biomarker stage leads into the ataxia stage, defined by manifest ataxia. The present analysis provides a robust framework for further studies aiming at elaboration and differentiation of the staging model of SCA3., Competing Interests: GO consults for IXICO Technologies Limited, which provides neuroimaging services and digital biomarker analytics to biopharmaceutical firms conducting clinical trials for SCAs, and receives research support from Biogen, which develops therapeutics for SCAs. MS has received consultancy honoraria from Janssen, Ionis, Orphazyme, Servier, Reata, GenOrph, and AviadoBio, all unrelated to the present manuscript. LS received consultancy honoraria from Vico Therapeutics and Novartis unrelated to the present manuscript. LPA research group has private funding from PTC Therapeutics, Uniqure, Wave life Sciences, Servier, Blade Therapeutics and Hoffmann-La Roche AG outside the submitted work.
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- 2023
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