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Preclinical research

Members of the committee

Yann Herault

William Mobley

Lizzy Fisher

Marie-Claude Potier

Stylianos Antonarakis

Jean Maurice Delabar

Eugene Yu

Katheleen Gardiner

 

Useful links

Bibliography

link provided by Dr J Florez (Fundación Iberoamericana Down21)

http://www.down21.org/web_n/index.php?option=com_wrapper&view=wrapper&Itemid=166

http://downciclopedia.org/areas/resumenes-bibliograficos

http://www.downciclopedia.org/areas/resumenes-bibliograficos

"Sindrome de Down: Neurobiologia, Neuropsicologia, Salud mental", editors: Jesus Florez, Beatriz Garvia, Roser Fernandez-Olaria in Ciencias de la Educacion Preescolar y Especial

 

Frontiers in Behavioral Neuroscience

Research Topic: Intellectual Disabilities in Down Syndrome from Birth and Throughout Life: Assessment and Treatment

Research on the multiple aspects of cognitive impairment in Down syndrome (DS), from genes to behavior to treatment, has made tremendous progress in the last decade. The study of congenital intellectual disabilities such as DS is challenging since they originate from the earliest stages of development and both the acquisition of cognitive skills and neurodegenerative pathologies are cumulative. Comorbidities such as cardiac malformations, sleep apnea, diabetes and dementia are frequent in the DS population, as well, and their increased risk provides a means of assessing early stages of these pathologies that is relevant to the general population. Notably, persons with DS will develop the histopathology of Alzheimer’s disease (formation of neuritic plaques and tangles) and are at high risk for dementia, something that cannot be predicted in the population at large. Identification of the gene encoding the amyloid precursor protein, its localization to chromosome 21 in the 90’s and realization that all persons with DS develop pathology identified this as an important piece of the amyloid cascade hypothesis in Alzheimer’s disease. Awareness of the potential role of people with DS in understanding progression and treatment as well as identification of genetic risk factors and also protective factors for AD is reawakening.


For the first time since DS was recognized, major pharmaceutical companies have entered the search for ameliorative treatments, and phase II clinical trials to improve learning and memory are in progress. Enriched environment, brain stimulation and alternative therapies are being tested while clinical assessment is improving, thus increasing the chances of success for therapeutic interventions. Researchers and clinicians are actively pursuing the possibility of prenatal treatments for many conditions, an area with a huge potential impact for developmental disorders such as DS.
Our goal here is to present an overview of recent advances with an emphasis on behavioral and cognitive deficits and how these issues change through life in DS. The relevance of comorbidities to the end phenotypes described and relevance of pharmacological targets and possible treatments will be considerations throughout.

Dissecting Alzheimer disease in Down syndrome using mouse models

Pharmacological correction of excitation/inhibition imbalance in Down syndrome mouse models

Principal Component Analysis of the Effects of Environmental Enrichment and (-)-epigallocatechin-3-gallate on Age-Associated Learning Deficits in a Mouse Model of Down Syndrome

DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome

 

Virtual laboratory:

https://21lab.ucsd.edu/

 

Resources provided by the committee

1. Mouse models for Down Syndrome resesarch

Commonly used models. Please contact the Chair of the Preclinicial Committee for additions or edits.

2. Treatment for DS mice models

In the last ten years, there has been a dramatic increase in research efforts focused on therapeutic interventions to rescue the brain phenotype and improve learning/memory. These experiments have mainly used adult Ts65Dn mice however other models with partial trisomy or trisomy of a single gene are now also studied. These approaches are based upon different strategies: cell therapy, environmental enrichment, single gene targeting, oxidative stress, inhibitory/excitatory balance, neurotransmitters and other pharmacologically based strategies. The table (accessible by clicking on "downloads" after log-in in to the T21RS Membership Environment) has been built from recent original papers and reviews (Guedj et al, 2014; Ciani et al, 2015). This table will be complemented with new results (published or not) and should be also used as a storage tool for information on failed treatments.