Evidence map›Paper›PMID 31980808›Full record

ReviewNature reviews. Neurology2020

LRRK2 in Parkinson disease: challenges of clinical trials.

Eduardo Tolosa, Miquel Vila, Christine Klein, Olivier Rascol

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 275 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
275citing papers in PubMed, 5 pooled it
25.2field-weighted citation impact, top 1% of its field
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

275 citing papers in PubMed, 5 syntheses or guidelines pooled it, 445 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Underrepresented Populations in Parkinson's Genetics Research: Current Landscape and Future Directions.Movement disorders : official journal of the Movement Disorder Society · 2022
    Pooled it
  4. Pooled it
  5. Coding and Noncoding Variation in LRRK2 and Parkinson's Disease Risk.Movement disorders : official journal of the Movement Disorder Society · 2022
    Pooled it
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Ex Vivo LRRK2 Activation in Asian G2385R and R1628P Variant Carriers and Idiopathic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  17. Article
  18. Review
  19. Emerging directions in tauopathy research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  20. Elucidating the molecular interplay between LRRK2 and Rab GTPases.bioRxiv : the preprint server for biology · 2026
    Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 4 institutions in 3 countries.

Eduardo TolosaParkinson and Movement Disorders Unit, Neurology Service, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain. etolosa@clinic.cat.ORCID http://orcid.org/0000-0002-3781-0854
Miquel VilaNetwork Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.
Christine KleinInstitute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Olivier RascolClinical Investigation Center CIC1436, Departments of Clinical Pharmacology and Neurosciences, NS-Park/FCRIN network and NeuroToul Center of Excellence for Neurodegeneration, INSERM, University Hospital of Toulouse and University of Toulouse, Toulouse, France.
Biomedical Research Networking Center on Neurodegenerative Diseases · ESInserm · FRInstitució Catalana de Recerca i Estudis Avançats · ESUniversity of Lübeck · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

One of the most common monogenic forms of Parkinson disease (PD) is caused by mutations in the LRRK2 gene that encodes leucine-rich repeat kinase 2 (LRRK2). LRRK2 mutations, and particularly the most common mutation Gly2019Ser, are observed in patients with autosomal dominant PD and in those with apparent sporadic PD, who are clinically indistinguishable from those with idiopathic PD. The discoveries that pathogenic mutations in the LRRK2 gene increase LRRK2 kinase activity and that small-molecule LRRK2 kinase inhibitors can be neuroprotective in preclinical models of PD have placed LRRK2 at the centre of disease modification efforts in PD. Recent investigations also suggest that LRRK2 has a role in the pathogenesis of idiopathic PD and that LRRK2 therapies might, therefore, be beneficial in this common subtype of PD. In this Review, we describe the characteristics of LRRK2-associated PD that are most relevant to the development of LRRK2-targeted therapies and the design and implementation of clinical trials. We highlight strategies for correcting the effects of mutations in the LRRK2 gene, focusing on how to identify which patients are the optimal candidates and how to decide on the timing of such trials. In addition, we discuss challenges in implementing trials of disease-modifying treatment in people who carry LRRK2 mutations.

Indexed as

Antiparkinson AgentsClinical Trials as TopicHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Parkinson DiseaseAntiparkinson AgentsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, human

Identifiers

PMID31980808
OpenAlexW3001241789

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.