Affiliation:
1. Centre for Genomic Regulation The Barcelona Institute of Science and Technology Barcelona Spain
2. Universitat Pompeu Fabra Barcelona Spain
3. Integrative Pharmacology and Systems Neurosciences Research Group, Neurosciences Research Program Hospital del Mar Medical Research Institute Barcelona Spain
4. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición Instituto de Salud Carlos III Madrid Spain
5. Centro de Investigación Biomédica en Red de Enfermedades Raras Barcelona Spain
Abstract
AbstractIn 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.
Funder
Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
EU Joint Programme – Neurodegenerative Disease Research
H2020 Excellent Science
NIH Blueprint for Neuroscience Research
Generalitat de Catalunya
Agencia Estatal de Investigación
European Commission
Horizon 2020 Framework Programme
Ministerio de Ciencia e Innovación
Fondation Jérôme Lejeune
Subject
Neurology (clinical),Developmental Neuroscience,Pediatrics, Perinatology and Child Health
Cited by
7 articles.
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