Members of the committee
Jean Maurice Delabar
link provided by Dr J Florez (Fundación Iberoamericana Down21)
"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 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.
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). The first table was established in 2015. An updated version (2019) is available and it will be complemented with new results (published or not); it should be also used as a storage tool for information on failed treatments.