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Cited by 22Down syndrome and intellectual disability researchAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

State-of-the-art therapy for down syndrome

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Lorenzon, Nicola, Musoles‐Lleó, Juanluis, Turrisi, Federica, Gomis‐González, Maria, De La Torre, Rafael, Dierssen, Mara·2023·Developmental Medicine & Child Neurology
DOI 10.1111/dmcn.15517
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Abstract

In the last decade, an important effort was made in the field of Down syndrome to find new interventions that improve cognition. These therapies have added to the traditional symptomatic treatments and to the drugs for treating Alzheimer disease in the general population repurposed for Down syndrome. Defining next‐generation therapeutics will involve biomarker‐based therapeutic decision‐making, and preventive and multimodal interventions. However, translation of specific findings into effective therapeutic strategies has been disappointingly slow and has failed in many cases at the clinical level, leading to reduced credibility of mouse studies. This is aggravated by a tendency to favour large‐magnitude effects and highly significant findings, leading to high expectations but also to a biased view of the complex pathophysiology of Down syndrome. Here, we review some of the most recent and promising strategies for ameliorating the cognitive state of individuals with Down syndrome. We studied the landscape of preclinical and clinical studies and conducted a thorough literature search on PubMed and ClinicalTrials.gov for articles published between June 2012 and August 2022 on therapies for ameliorating cognitive function in individuals with Down syndrome. We critically assess current therapeutic approaches, why therapies fail in clinical trials in Down syndrome, and what could be the path forward. We discuss some intrinsic difficulties for translational research, and the need for a framework that improves the detection of drug efficacy to avoid discarding compounds too early from the companies’ pipelines.

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  • The majority of therapeutics to date administered to Ts65Dn mice across ages have targeted specific neurotransmitter systems or aberrant neural pathways, based on their contribution to cognitive and behavioral phenotypes.

    “The majority of therapeutics to date administered to Ts65Dn mice across ages have targeted specific neurotransmitter systems or aberrant neural pathways, based on their contribution to cognitive and behavioral phenotypes (Lorenzon et al., 2023).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Lorenzon et al., 2023

    In “What this paper adds” (page unavailable), the review says neurotransmitter-based therapies were long the most popular symptomatic treatments and links neurotransmitter dysfunction to cognitive impairment in Down syndrome. Its account of preclinical research concerns Down syndrome mouse models generally; it does not establish that a majority of treatments administered to Ts65Dn mice across ages targeted neurotransmitter systems or aberrant neural pathways. (LLM, conf=0.85)

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Cited by

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Authors
Lorenzon, N., Musoles‐Lleó, J., Turrisi, F., Gomis‐González, M., De La Torre, R., & Dierssen, M.
Affiliations
  • Centre for Genomic Regulation The Barcelona Institute of Science and Technology Barcelona Spain
  • Universitat Pompeu Fabra (ES)
  • Hospital Del Mar (ES)
  • Universitat Pompeu Fabra Barcelona Spain
Corresponding author
Dierssen, Mara
ORCID
Venue
Developmental Medicine & Child Neurology
Publisher
Wiley
Published
2023-01-24
Volume
65
Issue
7
Pages
870-884
ISSN
  • 0012-1622 (ISSN-L)
  • 1469-8749
DOI
10.1111/dmcn.15517
OpenAlex
W4317868764
Cited by
22
References
4
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 2
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Developmental Medicine & Child Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya (2017 SGR 138)
  • EU Joint Programme – Neurodegenerative Disease Research (AC170006)
  • H2020 Excellent Science (848077, 899986)
  • NIH Blueprint for Neuroscience Research (1R01EB 028159‐01)
  • Generalitat de Catalunya
  • Agencia Estatal de Investigación (PID2019‐110755RB‐I00/AEI/10.13039/501100011033)
  • European Commission
  • Horizon 2020 Framework Programme
  • Ministerio de Ciencia e Innovación
  • Fondation Jérôme Lejeune
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Down syndrome, cognitive impairment, therapeutic interventions, biomarkers, translational research, clinical trial failure, mouse model, multimodal intervention
MeSH terms
Alzheimer Disease, Animals, Down Syndrome, Humans, Mice

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