Evidence map›Paper›PMID 35716693›Full record

ReviewThe Lancet. Neurology2022

A biological classification of Huntington's disease: the Integrated Staging System.

Sarah J Tabrizi, Scott Schobel, Emily C Gantman, Alexandra Mansbach, Beth Borowsky, Pavlina Konstantinova, Tiago A Mestre, Jennifer Panagoulias, Christopher A Ross, Maurice Zauderer and 7 more

Abstract readReview
PubMed Publisher
In one paragraph

Review in The Lancet. Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 3 pooled it
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

179 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Systematic Review of the Huntington's Disease Drug Development Pipeline, 2014 to 2025.Movement disorders : official journal of the Movement Disorder Society · 2026
    Pooled it
  2. Systematic Review with Meta-Analysis of Biofluid Markers for Huntington's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Article
  7. Stage-dependent tau-PET signatures in Huntington's disease revealed by [¹⁸F]PI-2620.European journal of nuclear medicine and molecular imaging · 2026
    Article
  8. Review
  9. Article
  10. Fluid and Imaging Biomarkers in Huntington's Disease.Current neurology and neuroscience reports · 2026
    Review
  11. Article
  12. Article
  13. Observational
  14. Article
  15. Article
  16. Article
  17. Toward the prevention of clinically manifest Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  18. Review
  19. Article
  20. Article

119 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Sarah J TabriziUCL Huntington's Disease Centre, Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, UK Dementia Research Institute, University College London, UK. Electronic address: s.tabrizi@ucl.ac.uk.
Scott SchobelProduct Development Neuroscience, F Hoffmann-La Roche, Basel, Switzerland.
Emily C GantmanCHDI Management/CHDI Foundation, Princeton, NJ, USA.
Alexandra MansbachAPS Consulting Services, Washington, DC, USA.
Beth BorowskyNovartis Pharmaceuticals, East Hanover, NJ, USA.
Pavlina KonstantinovaVectorY BV, Amsterdam, Netherlands.
Tiago A MestreParkinson's Disease and Movement Disorders Centre, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada.
Jennifer PanagouliasWave Life Sciences, Cambridge, MA, USA.
Christopher A RossDivision of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Departments of Neurology, Neuroscience, and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Maurice ZaudererVaccinex, Rochester, NY, USA.
Ariana P MullinWave Life Sciences, Cambridge, MA, USA.
Klaus RomeroCritical Path Institute, Tucson, Arizona 85718, USA.
Sudhir SivakumaranCritical Path Institute, Tucson, Arizona 85718, USA.
Emily C TurnerCritical Path Institute, Tucson, Arizona 85718, USA.
Jeffrey D LongDepartment of Psychiatry, Department of Biostatistics, University of Iowa, Iowa City, IA, USA.
Cristina SampaioCHDI Management/CHDI Foundation, Princeton, NJ, USA; Clinical Pharmacology Laboratory, Faculdade de Medicina de Lisboa, University of Lisbon, Lisbon, Portugal. Electronic address: cristina.sampaio@chdifoundation.org.
Huntington's Disease Regulatory Science Consortium (HD-RSC)

Funding

Validation of Novel Pathogenic Post-Translational Modifications of Huntingtin, and of Modifying Enzymes as Therapeutic Targets for Huntington's DiseaseR01NS086452 · NINDS · JOHNS HOPKINS UNIVERSITY · PI ROSS, CHRISTOPHER A · 2014 to 2023
$6.2M
FDA HHS U18 FD005320NINDS NIH HHS R01 NS086452Wellcome Trust 200181/Z/15/Z
6 · The paper itself

Abstract

The current research paradigm for Huntington's disease is based on participants with overt clinical phenotypes and does not address its pathophysiology nor the biomarker changes that can precede by decades the functional decline. We have generated a new research framework to standardise clinical research and enable interventional studies earlier in the disease course. The Huntington's Disease Integrated Staging System (HD-ISS) comprises a biological research definition and evidence-based staging centred on biological, clinical, and functional assessments. We used a formal consensus method that involved representatives from academia, industry, and non-profit organisations. The HD-ISS characterises individuals for research purposes from birth, starting at Stage 0 (ie, individuals with the Huntington's disease genetic mutation without any detectable pathological change) by using a genetic definition of Huntington's disease. Huntington's disease progression is then marked by measurable indicators of underlying pathophysiology (Stage 1), a detectable clinical phenotype (Stage 2), and then decline in function (Stage 3). Individuals can be precisely classified into stages based on thresholds of stage-specific landmark assessments. We also demonstrated the internal validity of this system. The adoption of the HD-ISS could facilitate the design of clinical trials targeting populations before clinical motor diagnosis and enable data standardisation across ongoing and future studies.

Indexed as

Huntington DiseaseDisease ProgressionHumansLongitudinal StudiesPhenotype

Identifiers

PMID35716693

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.