Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society

Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6–9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitive and behavioral challenges and better understand comorbidities associated with Down syndrome, including Alzheimer’s disease and leukemia. Presentation of cutting-edge results in neuroscience, neurology, model systems, psychology, cancer, biomarkers and molecular and pharmacological therapeutic approaches demonstrate the compelling interest and continuing advancement in all aspects of understanding and ameliorating conditions associated with T21.

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Changing Paradigms in Down Syndrome: The First International Conference of the Trisomy 21 Research Society

Molecular Syndromology ◽

10.1159/000449049 ◽

2016 ◽

Vol 7 (5) ◽

pp. 251-261 ◽

Cited By ~ 3

Author(s):

Jean-Maurice Delabar ◽

Bernadette Allinquant ◽

Diana Bianchi ◽

Tom Blumenthal ◽

Alain Dekker ◽

...

Keyword(s):

Down Syndrome ◽

Trisomy 21 ◽

Research Society ◽

International Conference

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Medical vulnerability of individuals with Down syndrome to severe COVID-19–data from the Trisomy 21 Research Society and the UK ISARIC4C survey

EClinicalMedicine ◽

10.1016/j.eclinm.2021.100769 ◽

2021 ◽

Vol 33 ◽

pp. 100769 ◽

Cited By ~ 2

Author(s):

Anke Hüls ◽

Alberto C.S. Costa ◽

Mara Dierssen ◽

R. Asaad Baksh ◽

Stefania Bargagna ◽

...

Keyword(s):

Down Syndrome ◽

Trisomy 21 ◽

Research Society ◽

The Uk

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Paving the Way for Therapy: The Second International Conference of the Trisomy 21 Research Society

Molecular Syndromology ◽

10.1159/000494231 ◽

2018 ◽

Vol 9 (6) ◽

pp. 279-286 ◽

Cited By ~ 3

Author(s):

Roger H. Reeves ◽

Jean Delabar ◽

Marie-Claude Potier ◽

Anita Bhattacharyya ◽

Elizabeth Head ◽

...

Keyword(s):

Trisomy 21 ◽

Research Society ◽

International Conference ◽

The Way ◽

Second International

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Identification of dysregulated genes in lymphocytes from children with Down syndrome

Genome ◽

10.1139/g07-100 ◽

2008 ◽

Vol 51 (1) ◽

pp. 19-29 ◽

Cited By ~ 28

Author(s):

Cesar A. Sommer ◽

Erika C. Pavarino-Bertelli ◽

Eny M. Goloni-Bertollo ◽

Flavio Henrique-Silva

Keyword(s):

Gene Expression ◽

Down Syndrome ◽

Trisomy 21 ◽

Molecular Mechanisms ◽

Cell Types ◽

Cell Receptor ◽

Chromosome 21 ◽

Global Changes ◽

Real Time Quantitative Pcr ◽

Functional Classes

The molecular mechanisms by which trisomy of human chromosome 21 disrupts normal development are not well understood. Global transcriptome studies attempting to analyze the consequences of trisomy in Down syndrome (DS) tissues have reported conflicting results, which have led to the suggestion that the analysis of specific tissues or cell types may be more productive. In the present study, we set out to analyze global changes of gene expression in lymphocytes from children with trisomy 21 by means of the serial analysis of gene expression (SAGE) methodology. Two SAGE libraries were constructed using pooled RNA of normal and Down syndrome children. Comparison between DS and normal profiles revealed that most of the transcripts were expressed at similar levels and functional classes of abundant genes were equally represented. Among the 242 significantly differentially expressed SAGE tags, several transcripts downregulated in DS code for proteins involved in T-cell and B-cell receptor signaling (e.g., PI3Kδ, RGS2, LY6E, FOS, TAGAP, CD46). The SAGE data and interindividual variability were validated by real-time quantitative PCR. Our results indicate that trisomy 21 induces a modest dysregulation of disomic genes that may be related to the immunological perturbations seen in DS.

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Prenatal and Postnatal Pharmacotherapy in Down Syndrome: The Search to Prevent or Ameliorate Neurodevelopmental and Neurodegenerative Disorders

The Annual Review of Pharmacology and Toxicology ◽

10.1146/annurev-pharmtox-041521-103641 ◽

2022 ◽

Vol 62 (1) ◽

pp. 211-233

Author(s):

Renata Bartesaghi ◽

Stefano Vicari ◽

William C. Mobley

Keyword(s):

Down Syndrome ◽

Neurodegenerative Disorders ◽

Research Agenda ◽

Behavioral Changes ◽

Model Systems ◽

Chromosome 21 ◽

Rodent Models ◽

Cell Models ◽

Behavioral Challenges ◽

And Behavior

Those with Down syndrome (DS)—trisomy for chromosome 21—are routinely impacted by cognitive dysfunction and behavioral challenges in children and adults and Alzheimer's disease in older adults. No proven treatments specifically address these cognitive or behavioral changes. However, advances in the establishment of rodent models and human cell models promise to support development of such treatments. A research agenda that emphasizes the identification of overexpressed genes that contribute demonstrably to abnormalities in cognition and behavior in model systems constitutes a rational next step. Normalizing expression of such genes may usher in an era of successful treatments applicable across the life span for those with DS.

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Blood vessel differentiation and growth

10.1093/med/9780198757269.003.0016 ◽

2018 ◽

Author(s):

Rui Benedito ◽

Arndt F. Siekmann

Keyword(s):

Vascular Function ◽

Molecular Mechanisms ◽

Vascular System ◽

Evolutionary Conservation ◽

Model Systems ◽

Molecular Pathways ◽

Life And Death ◽

Cellular Processes ◽

Origin Life ◽

Lines Of Evidence

A variety of diseases are related to or dependent on the vascular system. Several lines of evidence show that adequate manipulation of the vascular function in disease requires targeting and interfering with the same molecular pathways and cellular processes that act to form vessels during embryo or organ development. Therefore an understanding of the mechanisms that regulate vascular development in this non-pathological context is of major importance, since it may lead to better ways of treating vascular-related pathologies. This chapter covers the most significant cellular and molecular mechanisms involved in the origin, life, and death of the endothelial cellwhich is involved in several important developmental and pathological processes. Most of the mechanisms described were identified in animal model systems. However, owing to the high evolutionary conservation of these, they are likely be very similar to those occurring in humans and in disease.

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Comparison of COVID-19 and Non-COVID-19 Pneumonia in Down Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm10163748 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3748

Author(s):

Diego Real de Asua ◽

Miguel A. Mayer ◽

María del Carmen Ortega ◽

Jose M. Borrel ◽

Teresa de Jesús Bermejo ◽

...

Keyword(s):

Down Syndrome ◽

Cohort Study ◽

Trisomy 21 ◽

Retrospective Cohort ◽

Mortality Rates ◽

Research Society ◽

Clinical Database ◽

Increased Risk ◽

The Mean ◽

Disease Specific

Whether the increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death observed in Down syndrome (DS) are disease specific or also occur in individuals with DS and non-COVID-19 pneumonias is unknown. This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey (n = 86) with admissions for non-COVID-19 pneumonias from a retrospective clinical database of the Spanish Ministry of Health (n = 2832 patients). In-hospital mortality rates were significantly higher for COVID-19 patients (26.7% vs. 9.4%), especially among individuals over 40 and patients with obesity, dementia, and/or epilepsy. The mean length of stay of deceased patients with COVID-19 was significantly shorter than in those with non-COVID-19 pneumonias. The rate of admission to an ICU in patients with DS and COVID-19 (4.3%) was significantly lower than that reported for the general population with COVID-19. Our findings confirm that acute SARS-CoV-2 infection leads to higher mortality than non-COVID-19 pneumonias in individuals with DS, especially among adults over 40 and those with specific comorbidities. However, differences in access to respiratory support might also account for some of the heightened mortality of individuals with DS with COVID-19.

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