Evidence map›Paper›PMID 36190676›Full record

ArticleCerebellum (London, England)2024

Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping.

Alain Ndayisaba, Ariana T Pitaro, Andrew S Willett, Kristie A Jones, Claudio Melo de Gusmao, Abby L Olsen, Jisoo Kim, Eero Rissanen, Jared K Woods, Sharan R Srinivasan and 41 more

Erratum issued Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cerebellum (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06868628 (A Phase 2a Study to Evaluate Microglial Activation, Safety, and Clinical Effects of Foralumab Nasal in Patients With Multiple System Atrophy), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06868628 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

A Phase 2a Study to Evaluate Microglial Activation, Safety, and Clinical Effects of Foralumab Nasal in Patients With Multiple System Atrophy (MSA)

TypeinterventionalSponsorTiziana Life Sciences LTDRan2025 to 2027Enrolled5ConditionsMultiple System AtrophyArmsForalumab Nasal
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Cytotoxic T cell recognition of α-synuclein drives pathogenic immune responses in multiple system atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

51 authors.

Alain NdayisabaDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Ariana T PitaroDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Andrew S WillettDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Kristie A JonesDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Claudio Melo de GusmaoDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Abby L OlsenDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Jisoo KimDepartment of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Eero RissanenDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Jared K WoodsDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Sharan R SrinivasanDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Anna NagyDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Amanda NagyDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Merlyne MesidorDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Steven CiceroDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Viharkumar PatelDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Derek H OakleyDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Idil TuncaliDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Katherine Taglieri-NobleDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Emily C ClarkDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Jordan PaulsonDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Richard C KrolewskiDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Gary P HoDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Albert Y HungDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Anne-Marie WillsDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Michael T HayesDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Jason P MacmoreDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Luigi WarrenCellular Reprogramming, Inc., Pasadena, CA, USA.
Pamela G BowerThe Multiple System Atrophy Coalition, Inc., 7918 Jones Branch Drive, Suite 300, McLean, VA, 22102, USA.
Carol B LangerThe Multiple System Atrophy Coalition, Inc., 7918 Jones Branch Drive, Suite 300, McLean, VA, 22102, USA.
Lawrence R KellermanThe Multiple System Atrophy Coalition, Inc., 7918 Jones Branch Drive, Suite 300, McLean, VA, 22102, USA.
Christopher W HumphreysDepartment of Pulmonary, Sleep and Critical Care Medicine, Salem Hospital, MassGeneral Brigham, Salem, MA, 01970, USA.
Bonnie I GlanzDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Elodi J DielubanzaDepartment of Urology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Matthew P FroschDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Roy L FreemanDepartment of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02115, USA.
Christopher H GibbonsDepartment of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02115, USA.
Nadia StefanovaDivision of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Tanuja ChitnisDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Howard L WeinerDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Clemens R ScherzerDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Sonja W ScholzLaboratory of Neurogenetics, Disorders and Stroke, National Institute of Neurological, National Institute of Neurological Disorders and Stroke, Bethesda, MD, 20892, USA.
Dana VuzmanDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Laura M CoxDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Gregor WenningDivision of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Jeremy D SchmahmannDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Anoopum S GuptaDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Peter NovakDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Geoffrey S YoungDepartment of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Mel B FeanyDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Tarun SinghalDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
Vikram KhuranaDepartment of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA. vkhurana@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-4018-5527

Funding

The Southwest National Primate Research Center Supplement- Infrastructure improvements of ABSL2 holding areasP51OD011133 · OD · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI Larry S. Schlesinger · 2012 to 2026
$129.7M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Elucidating the Biological Differences Between Distinct Fibrillar and Non-Fibrillar Alpha-Synuclein Inclusions in Human Stem-Cell ModelsR01NS109209 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KHURANA, VIKRAM · 2020 to 2024
$4.5M
Genome-Wide Prediction of Dementia in Parkinson's DiseaseR01NS115144 · NINDS · YALE UNIVERSITY · PI SCHERZER, CLEMENS R · 2019 to 2025
$4.4M
Oncopathology Training ProgramT32CA251062 · NCI · DANA-FARBER CANCER INST · PI JON C. ASTER, KATHLEEN H BURNS · 2020 to 2026
$2.4M
NCI NIH HHS T32 CA251062NIA NIH HHS P30 AG062421NIH HHS 1R01NS109209-01A1NIH HHS P51 OD011133NINDS NIH HHS R01 NS109209NINDS NIH HHS R01 NS115144
6 · The paper itself

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.

Indexed as

Induced Pluripotent Stem CellsMultiple System AtrophyParkinson Diseasealpha-SynucleinAnimalsBrainHumansReceptors, GABAalpha-SynucleinReceptors, GABATSPO protein, humanClinical trialsInduced pluripotent stem cellsMultiple system atrophyN-of-1 clinical trialsStratification

Identifiers

PMID36190676
PMCPMC9527378

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.