Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping
Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked inter...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Ndayisaba, Alain [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2022. corrected publication 2022 |
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| Übergeordnetes Werk: |
Enthalten in: The Cerebellum - London : Dunitz, 2002, 23(2022), 1 vom: 03. Okt., Seite 31-51 |
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| Übergeordnetes Werk: |
volume:23 ; year:2022 ; number:1 ; day:03 ; month:10 ; pages:31-51 |
| Links: |
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| DOI / URN: |
10.1007/s12311-022-01471-8 |
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SPR054753090 |
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| 520 | |a Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. | ||
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| 650 | 4 | |a Stratification |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Clinical trials |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a N-of-1 clinical trials |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Induced pluripotent stem cells |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Willett, Andrew S. |4 aut | |
| 700 | 1 | |a Jones, Kristie A. |4 aut | |
| 700 | 1 | |a de Gusmao, Claudio Melo |4 aut | |
| 700 | 1 | |a Olsen, Abby L. |4 aut | |
| 700 | 1 | |a Kim, Jisoo |4 aut | |
| 700 | 1 | |a Rissanen, Eero |4 aut | |
| 700 | 1 | |a Woods, Jared K. |4 aut | |
| 700 | 1 | |a Srinivasan, Sharan R. |4 aut | |
| 700 | 1 | |a Nagy, Anna |4 aut | |
| 700 | 1 | |a Nagy, Amanda |4 aut | |
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10.1007/s12311-022-01471-8 doi (DE-627)SPR054753090 (SPR)s12311-022-01471-8-e DE-627 ger DE-627 rakwb eng Ndayisaba, Alain verfasserin aut Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022. corrected publication 2022 Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. Multiple system atrophy (dpeaa)DE-He213 Stratification (dpeaa)DE-He213 Clinical trials (dpeaa)DE-He213 N-of-1 clinical trials (dpeaa)DE-He213 Induced pluripotent stem cells (dpeaa)DE-He213 Pitaro, Ariana T. aut Willett, Andrew S. aut Jones, Kristie A. aut de Gusmao, Claudio Melo aut Olsen, Abby L. aut Kim, Jisoo aut Rissanen, Eero aut Woods, Jared K. aut Srinivasan, Sharan R. aut Nagy, Anna aut Nagy, Amanda aut Mesidor, Merlyne aut Cicero, Steven aut Patel, Viharkumar aut Oakley, Derek H. aut Tuncali, Idil aut Taglieri-Noble, Katherine aut Clark, Emily C. aut Paulson, Jordan aut Krolewski, Richard C. aut Ho, Gary P. aut Hung, Albert Y. aut Wills, Anne-Marie aut Hayes, Michael T. aut Macmore, Jason P. aut Warren, Luigi aut Bower, Pamela G. aut Langer, Carol B. aut Kellerman, Lawrence R. aut Humphreys, Christopher W. aut Glanz, Bonnie I. aut Dielubanza, Elodi J. aut Frosch, Matthew P. aut Freeman, Roy L. aut Gibbons, Christopher H. aut Stefanova, Nadia aut Chitnis, Tanuja aut Weiner, Howard L. aut Scherzer, Clemens R. aut Scholz, Sonja W. aut Vuzman, Dana aut Cox, Laura M. aut Wenning, Gregor aut Schmahmann, Jeremy D. aut Gupta, Anoopum S. aut Novak, Peter aut Young, Geoffrey S. aut Feany, Mel B. aut Singhal, Tarun aut Khurana, Vikram (orcid)0000-0002-4018-5527 aut Enthalten in The Cerebellum London : Dunitz, 2002 23(2022), 1 vom: 03. Okt., Seite 31-51 (DE-627)342317237 (DE-600)2071266-2 1473-4230 nnns volume:23 year:2022 number:1 day:03 month:10 pages:31-51 https://dx.doi.org/10.1007/s12311-022-01471-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 23 2022 1 03 10 31-51 |
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10.1007/s12311-022-01471-8 doi (DE-627)SPR054753090 (SPR)s12311-022-01471-8-e DE-627 ger DE-627 rakwb eng Ndayisaba, Alain verfasserin aut Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022. corrected publication 2022 Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. Multiple system atrophy (dpeaa)DE-He213 Stratification (dpeaa)DE-He213 Clinical trials (dpeaa)DE-He213 N-of-1 clinical trials (dpeaa)DE-He213 Induced pluripotent stem cells (dpeaa)DE-He213 Pitaro, Ariana T. aut Willett, Andrew S. aut Jones, Kristie A. aut de Gusmao, Claudio Melo aut Olsen, Abby L. aut Kim, Jisoo aut Rissanen, Eero aut Woods, Jared K. aut Srinivasan, Sharan R. aut Nagy, Anna aut Nagy, Amanda aut Mesidor, Merlyne aut Cicero, Steven aut Patel, Viharkumar aut Oakley, Derek H. aut Tuncali, Idil aut Taglieri-Noble, Katherine aut Clark, Emily C. aut Paulson, Jordan aut Krolewski, Richard C. aut Ho, Gary P. aut Hung, Albert Y. aut Wills, Anne-Marie aut Hayes, Michael T. aut Macmore, Jason P. aut Warren, Luigi aut Bower, Pamela G. aut Langer, Carol B. aut Kellerman, Lawrence R. aut Humphreys, Christopher W. aut Glanz, Bonnie I. aut Dielubanza, Elodi J. aut Frosch, Matthew P. aut Freeman, Roy L. aut Gibbons, Christopher H. aut Stefanova, Nadia aut Chitnis, Tanuja aut Weiner, Howard L. aut Scherzer, Clemens R. aut Scholz, Sonja W. aut Vuzman, Dana aut Cox, Laura M. aut Wenning, Gregor aut Schmahmann, Jeremy D. aut Gupta, Anoopum S. aut Novak, Peter aut Young, Geoffrey S. aut Feany, Mel B. aut Singhal, Tarun aut Khurana, Vikram (orcid)0000-0002-4018-5527 aut Enthalten in The Cerebellum London : Dunitz, 2002 23(2022), 1 vom: 03. Okt., Seite 31-51 (DE-627)342317237 (DE-600)2071266-2 1473-4230 nnns volume:23 year:2022 number:1 day:03 month:10 pages:31-51 https://dx.doi.org/10.1007/s12311-022-01471-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 23 2022 1 03 10 31-51 |
| allfields_unstemmed |
10.1007/s12311-022-01471-8 doi (DE-627)SPR054753090 (SPR)s12311-022-01471-8-e DE-627 ger DE-627 rakwb eng Ndayisaba, Alain verfasserin aut Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022. corrected publication 2022 Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. Multiple system atrophy (dpeaa)DE-He213 Stratification (dpeaa)DE-He213 Clinical trials (dpeaa)DE-He213 N-of-1 clinical trials (dpeaa)DE-He213 Induced pluripotent stem cells (dpeaa)DE-He213 Pitaro, Ariana T. aut Willett, Andrew S. aut Jones, Kristie A. aut de Gusmao, Claudio Melo aut Olsen, Abby L. aut Kim, Jisoo aut Rissanen, Eero aut Woods, Jared K. aut Srinivasan, Sharan R. aut Nagy, Anna aut Nagy, Amanda aut Mesidor, Merlyne aut Cicero, Steven aut Patel, Viharkumar aut Oakley, Derek H. aut Tuncali, Idil aut Taglieri-Noble, Katherine aut Clark, Emily C. aut Paulson, Jordan aut Krolewski, Richard C. aut Ho, Gary P. aut Hung, Albert Y. aut Wills, Anne-Marie aut Hayes, Michael T. aut Macmore, Jason P. aut Warren, Luigi aut Bower, Pamela G. aut Langer, Carol B. aut Kellerman, Lawrence R. aut Humphreys, Christopher W. aut Glanz, Bonnie I. aut Dielubanza, Elodi J. aut Frosch, Matthew P. aut Freeman, Roy L. aut Gibbons, Christopher H. aut Stefanova, Nadia aut Chitnis, Tanuja aut Weiner, Howard L. aut Scherzer, Clemens R. aut Scholz, Sonja W. aut Vuzman, Dana aut Cox, Laura M. aut Wenning, Gregor aut Schmahmann, Jeremy D. aut Gupta, Anoopum S. aut Novak, Peter aut Young, Geoffrey S. aut Feany, Mel B. aut Singhal, Tarun aut Khurana, Vikram (orcid)0000-0002-4018-5527 aut Enthalten in The Cerebellum London : Dunitz, 2002 23(2022), 1 vom: 03. Okt., Seite 31-51 (DE-627)342317237 (DE-600)2071266-2 1473-4230 nnns volume:23 year:2022 number:1 day:03 month:10 pages:31-51 https://dx.doi.org/10.1007/s12311-022-01471-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 23 2022 1 03 10 31-51 |
| allfieldsGer |
10.1007/s12311-022-01471-8 doi (DE-627)SPR054753090 (SPR)s12311-022-01471-8-e DE-627 ger DE-627 rakwb eng Ndayisaba, Alain verfasserin aut Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022. corrected publication 2022 Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. Multiple system atrophy (dpeaa)DE-He213 Stratification (dpeaa)DE-He213 Clinical trials (dpeaa)DE-He213 N-of-1 clinical trials (dpeaa)DE-He213 Induced pluripotent stem cells (dpeaa)DE-He213 Pitaro, Ariana T. aut Willett, Andrew S. aut Jones, Kristie A. aut de Gusmao, Claudio Melo aut Olsen, Abby L. aut Kim, Jisoo aut Rissanen, Eero aut Woods, Jared K. aut Srinivasan, Sharan R. aut Nagy, Anna aut Nagy, Amanda aut Mesidor, Merlyne aut Cicero, Steven aut Patel, Viharkumar aut Oakley, Derek H. aut Tuncali, Idil aut Taglieri-Noble, Katherine aut Clark, Emily C. aut Paulson, Jordan aut Krolewski, Richard C. aut Ho, Gary P. aut Hung, Albert Y. aut Wills, Anne-Marie aut Hayes, Michael T. aut Macmore, Jason P. aut Warren, Luigi aut Bower, Pamela G. aut Langer, Carol B. aut Kellerman, Lawrence R. aut Humphreys, Christopher W. aut Glanz, Bonnie I. aut Dielubanza, Elodi J. aut Frosch, Matthew P. aut Freeman, Roy L. aut Gibbons, Christopher H. aut Stefanova, Nadia aut Chitnis, Tanuja aut Weiner, Howard L. aut Scherzer, Clemens R. aut Scholz, Sonja W. aut Vuzman, Dana aut Cox, Laura M. aut Wenning, Gregor aut Schmahmann, Jeremy D. aut Gupta, Anoopum S. aut Novak, Peter aut Young, Geoffrey S. aut Feany, Mel B. aut Singhal, Tarun aut Khurana, Vikram (orcid)0000-0002-4018-5527 aut Enthalten in The Cerebellum London : Dunitz, 2002 23(2022), 1 vom: 03. Okt., Seite 31-51 (DE-627)342317237 (DE-600)2071266-2 1473-4230 nnns volume:23 year:2022 number:1 day:03 month:10 pages:31-51 https://dx.doi.org/10.1007/s12311-022-01471-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 23 2022 1 03 10 31-51 |
| allfieldsSound |
10.1007/s12311-022-01471-8 doi (DE-627)SPR054753090 (SPR)s12311-022-01471-8-e DE-627 ger DE-627 rakwb eng Ndayisaba, Alain verfasserin aut Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022. corrected publication 2022 Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. Multiple system atrophy (dpeaa)DE-He213 Stratification (dpeaa)DE-He213 Clinical trials (dpeaa)DE-He213 N-of-1 clinical trials (dpeaa)DE-He213 Induced pluripotent stem cells (dpeaa)DE-He213 Pitaro, Ariana T. aut Willett, Andrew S. aut Jones, Kristie A. aut de Gusmao, Claudio Melo aut Olsen, Abby L. aut Kim, Jisoo aut Rissanen, Eero aut Woods, Jared K. aut Srinivasan, Sharan R. aut Nagy, Anna aut Nagy, Amanda aut Mesidor, Merlyne aut Cicero, Steven aut Patel, Viharkumar aut Oakley, Derek H. aut Tuncali, Idil aut Taglieri-Noble, Katherine aut Clark, Emily C. aut Paulson, Jordan aut Krolewski, Richard C. aut Ho, Gary P. aut Hung, Albert Y. aut Wills, Anne-Marie aut Hayes, Michael T. aut Macmore, Jason P. aut Warren, Luigi aut Bower, Pamela G. aut Langer, Carol B. aut Kellerman, Lawrence R. aut Humphreys, Christopher W. aut Glanz, Bonnie I. aut Dielubanza, Elodi J. aut Frosch, Matthew P. aut Freeman, Roy L. aut Gibbons, Christopher H. aut Stefanova, Nadia aut Chitnis, Tanuja aut Weiner, Howard L. aut Scherzer, Clemens R. aut Scholz, Sonja W. aut Vuzman, Dana aut Cox, Laura M. aut Wenning, Gregor aut Schmahmann, Jeremy D. aut Gupta, Anoopum S. aut Novak, Peter aut Young, Geoffrey S. aut Feany, Mel B. aut Singhal, Tarun aut Khurana, Vikram (orcid)0000-0002-4018-5527 aut Enthalten in The Cerebellum London : Dunitz, 2002 23(2022), 1 vom: 03. 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Enthalten in The Cerebellum 23(2022), 1 vom: 03. Okt., Seite 31-51 volume:23 year:2022 number:1 day:03 month:10 pages:31-51 |
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Enthalten in The Cerebellum 23(2022), 1 vom: 03. Okt., Seite 31-51 volume:23 year:2022 number:1 day:03 month:10 pages:31-51 |
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Multiple system atrophy Stratification Clinical trials N-of-1 clinical trials Induced pluripotent stem cells |
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Ndayisaba, Alain @@aut@@ Pitaro, Ariana T. @@aut@@ Willett, Andrew S. @@aut@@ Jones, Kristie A. @@aut@@ de Gusmao, Claudio Melo @@aut@@ Olsen, Abby L. @@aut@@ Kim, Jisoo @@aut@@ Rissanen, Eero @@aut@@ Woods, Jared K. @@aut@@ Srinivasan, Sharan R. @@aut@@ Nagy, Anna @@aut@@ Nagy, Amanda @@aut@@ Mesidor, Merlyne @@aut@@ Cicero, Steven @@aut@@ Patel, Viharkumar @@aut@@ Oakley, Derek H. @@aut@@ Tuncali, Idil @@aut@@ Taglieri-Noble, Katherine @@aut@@ Clark, Emily C. @@aut@@ Paulson, Jordan @@aut@@ Krolewski, Richard C. @@aut@@ Ho, Gary P. @@aut@@ Hung, Albert Y. @@aut@@ Wills, Anne-Marie @@aut@@ Hayes, Michael T. @@aut@@ Macmore, Jason P. @@aut@@ Warren, Luigi @@aut@@ Bower, Pamela G. @@aut@@ Langer, Carol B. @@aut@@ Kellerman, Lawrence R. @@aut@@ Humphreys, Christopher W. @@aut@@ Glanz, Bonnie I. @@aut@@ Dielubanza, Elodi J. @@aut@@ Frosch, Matthew P. @@aut@@ Freeman, Roy L. @@aut@@ Gibbons, Christopher H. @@aut@@ Stefanova, Nadia @@aut@@ Chitnis, Tanuja @@aut@@ Weiner, Howard L. @@aut@@ Scherzer, Clemens R. @@aut@@ Scholz, Sonja W. @@aut@@ Vuzman, Dana @@aut@@ Cox, Laura M. @@aut@@ Wenning, Gregor @@aut@@ Schmahmann, Jeremy D. @@aut@@ Gupta, Anoopum S. @@aut@@ Novak, Peter @@aut@@ Young, Geoffrey S. @@aut@@ Feany, Mel B. @@aut@@ Singhal, Tarun @@aut@@ Khurana, Vikram @@aut@@ |
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2022-10-03T00:00:00Z |
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Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. 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Ndayisaba, Alain |
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Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping Multiple system atrophy (dpeaa)DE-He213 Stratification (dpeaa)DE-He213 Clinical trials (dpeaa)DE-He213 N-of-1 clinical trials (dpeaa)DE-He213 Induced pluripotent stem cells (dpeaa)DE-He213 |
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Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping |
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Ndayisaba, Alain Pitaro, Ariana T. Willett, Andrew S. Jones, Kristie A. de Gusmao, Claudio Melo Olsen, Abby L. Kim, Jisoo Rissanen, Eero Woods, Jared K. Srinivasan, Sharan R. Nagy, Anna Nagy, Amanda Mesidor, Merlyne Cicero, Steven Patel, Viharkumar Oakley, Derek H. Tuncali, Idil Taglieri-Noble, Katherine Clark, Emily C. Paulson, Jordan Krolewski, Richard C. Ho, Gary P. Hung, Albert Y. Wills, Anne-Marie Hayes, Michael T. Macmore, Jason P. Warren, Luigi Bower, Pamela G. Langer, Carol B. Kellerman, Lawrence R. Humphreys, Christopher W. Glanz, Bonnie I. Dielubanza, Elodi J. Frosch, Matthew P. Freeman, Roy L. Gibbons, Christopher H. Stefanova, Nadia Chitnis, Tanuja Weiner, Howard L. Scherzer, Clemens R. Scholz, Sonja W. Vuzman, Dana Cox, Laura M. Wenning, Gregor Schmahmann, Jeremy D. Gupta, Anoopum S. Novak, Peter Young, Geoffrey S. Feany, Mel B. Singhal, Tarun Khurana, Vikram |
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clinical trial-ready patient cohorts for multiple system atrophy: coupling biospecimen and ipsc banking to longitudinal deep-phenotyping |
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Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping |
| abstract |
Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. © The Author(s) 2022. corrected publication 2022 |
| abstractGer |
Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. © The Author(s) 2022. corrected publication 2022 |
| abstract_unstemmed |
Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson’s disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal “n-of-few” clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA. © The Author(s) 2022. corrected publication 2022 |
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Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping |
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| score |
7.403063 |