Targeting trisomic treatments: optimizing Dyrk1a inhibition to improve Down syndrome deficits

Abstract Overexpression of Dual‐specificity tyrosine‐phosphorylated regulated kinase 1A (DYRK1A), located on human chromosome 21, may alter molecular processes linked to developmental deficits in Down syndrome (DS). Trisomic DYRK1A is a rational therapeutic target, and although reductions in Dyrk1a genetic dosage have shown improvements in trisomic mouse models, attempts to reduce Dyrk1a activity by pharmacological mechanisms and correct these DS‐associated phenotypes have been largely unsuccessful. Epigallocatechin‐3‐gallate (EGCG) inhibits DYRK1A activity in vitro and this action has been postulated to account for improvement of some DS‐associated phenotypes that have been reported in preclinical studies and clinical trials. However, the beneficial effects of EGCG are inconsistent and there is no direct evidence that any observed improvement actually occurs through Dyrk1a inhibition. Inconclusive outcomes likely reflect a lack of knowledge about the tissue‐specific patterns of spatial and temporal overexpression and elevated activity of Dyrk1a that may contribute to emerging DS traits during development. Emerging evidence indicates that Dyrk1a expression varies over the life span in DS mouse models, yet preclinical therapeutic treatments targeting Dyrk1a have largely not considered these developmental changes. Therapies intended to improve DS phenotypes through normalizing trisomic Dyrk1a need to optimize the timing and dose of treatment to match the spat...
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: Review Article Source Type: research

Related Links:

Arthritis can be missed in young people with Down syndrome, who might not effectively communicate their pain, so experts recommend annual screening.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Rheumatology News Source Type: news
Conclusions and ImplicationsAlthough group differences were not found when considering parent-reported sleep problems, more frequent sleep problems were positively associated with increased forgetting by children with DS relative to those who were TD. Although future experimental work is needed to determine causality, these results suggest that improved sleep in children with DS might reduce forgetting, ultimately improving long-term recall memory.
Source: Research in Developmental Disabilities - Category: Disability Source Type: research
Abstract People with Down syndrome (DS) show dysfunction of gait, expressed by disturbed character of angular changes and values of the spatiotemporal parameters as compared to the physiological norm. It is known that exercises and various activities have positive effect on balance and gait, but there are only a few scientific proofs concerning above-mentioned in people with DS. Furthermore, the effect of Nordic Walking (NW) training on gait in people with DS is unexplored. We enrolled 22 subjects with DS, aged 25-40 years, with moderate intellectual disability. Participants were randomly divided into 2 groups: NW...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Conditions:   Down Syndrome;   Alzheimer Disease;   Dementia Intervention:   Sponsors:   University of Southern California;   National Institute on Aging (NIA);   Alzheimer's Clinical Trial Consortium;   Alzheimer's Therapeutic Research Institute Not yet recruiting
Source: - Category: Research Source Type: clinical trials
Global Down Syndrome Foundation president and CEO was one of DBJ's very first Outstanding Women in Business through her work in the cable industry.
Source: Health Care:Biotechnology headlines - Category: Biotechnology Authors: Source Type: news
Objective: The aim of the study was to analyze the long-term outcomes after cochlear implantation in deaf children with Down syndrome (DS) regarding age at the first implantation and refer the results to preoperative radiological findings as well as postoperative auditory and speech performance. Additionally, the influence of the age at implantation and duration of CI use on postoperative hearing and language skills were closely analyzed in children with DS. Study Design: Retrospective analysis. Setting: Referral center (Cochlear Implant Center). Materials and Methods: Nine children with Down syndrome were compa...
Source: Otology and Neurotology - Category: ENT & OMF Tags: COCHLEAR IMPLANTS Source Type: research
ConclusionsHealth-care professionals must be careful to speak in unprejudiced ways throughout the diagnostic process and present both termination and continuation of pregnancy as equally legitimate options. Nevertheless, the couples may still experience doubt and feel vulnerable following their decision to continue the pregnancy.
Source: Sexual and Reproductive Healthcare - Category: Reproduction Medicine Source Type: research
Source: Developmental Neurorehabilitation - Category: Neurology Authors: Source Type: research
(University of California - San Francisco) In a surprising finding using the standard animal model of Down syndrome (DS), scientists were able to correct the learning and memory deficits associated with the condition -- the leading genetic cause of cognitive disability and the most frequently diagnosed chromosomal disorder in the US -- with drugs that target the body's response to cellular stresses.
Source: EurekAlert! - Biology - Category: Biology Source Type: news
Publication date: 12 November 2019Source: Cell Reports, Volume 29, Issue 7Author(s): Katherine A. Waugh, Paula Araya, Ahwan Pandey, Kimberly R. Jordan, Keith P. Smith, Ross E. Granrath, Santosh Khanal, Eric T. Butcher, Belinda Enriquez Estrada, Angela L. Rachubinski, Jennifer A. McWilliams, Ross Minter, Tiana Dimasi, Kelley L. Colvin, Dmitry Baturin, Andrew T. Pham, Matthew D. Galbraith, Kyle W. Bartsch, Michael E. Yeager, Christopher C. PorterSummaryPeople with Down syndrome (DS; trisomy 21) display a different disease spectrum relative to the general population, including lower rates of solid malignancies and higher inci...
Source: Cell Reports - Category: Cytology Source Type: research
More News: Clinical Trials | Down's Syndrome | Genetics | Study