Page 81 - CIBERER2016-ENG

Most relevant scientific articles
• de la Torre R., de Sola S., Hernandez G., Farre M., Pujol J., Rodriguez J. et al. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down’s syndrome (TESDAD): A double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet Neurology. 2016;15(8):801-810.
• Ruiz-Mejias M., de Lagran M.M., Mattia M., Castano-Prat P., Perez-Mendez L., Ciria-Suarez L. et al. Overexpression of Dyrk1A, a down syndrome candidate, decreases excitability and impairs gamma oscillations in the prefrontal cortex. Journal of Neuroscience. 2016;36(13):3648-3659.
• Villanueva E., Marti-Solano M., Fillat C. Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness. Scientific Reports. 2016;6.
• Martinez-Bosch N., Guerrero P.E., Moreno M., Jose A., Iglesias M., Munne-Collado J. et al. The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer. Oncotarget. 2016;7(30):48265-48279.
• del Hoyo L., Xicota L., Langohr K., Sanchez-Benavides G., De Sola S., Cuenca-Royo A. et al. VNTR- DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in down syndrome. Frontiers in Behavioral Neuroscience. 2016;10(OCT).
Hightlights
The group focuses its research on the study of the molecular basis, the physiopathological mechanisms and therapeutical approaches of neurodevelopmental genetic diseases with a special interest on aneuploidies associated to human chromosome 21 (HSA21), and towards the development of therapeutic strategies for rare tumours and rare metabolic diseases, such as the glutaric aciduria.
In 2016, we have published the results of the phase 2 trial evaluating safety and efficacy of cognitive training plus epigallocatechin-3-gallate (EGCG) treatment in Down syndrome (DS) and fragile-X young adults.
An amelioration of the cognitive decline was observed after the combination treatment. To understand
the mechanisms that support these effects, we evaluated the impact of a combined environmental enrichment and EGCG therapy in the Ts65Dn mouse model of DS. An amelioration of the cognitive function was detected. Such improvements were accompanied by a rescue of CA1 dendritic spine density and a normalization of the proportion of excitatory and inhibitory synaptic markers in CA1 and dentate gyrus. Furthermore, during this year we have provided additional evidences supporting the role of DYRK1A in cognitive alterations in DS. These studies showed that an excess of DYRK1A in the prefrontal context led to functional deficits in the beta-gamma oscillations in the cortex due to alterations in the inhibitory activity. Regarding the development of novel therapies for the treatment of rare tumors, we have identified
a novel mechanism that adenoviruses use to optimize its activity in infected cells that have important consequences in the design of oncolytic adenoviruses. Moreover, we showed how tumor microenvironment interferes with the anti-neoplastic activity of receptor tyrosin kinase inhibitors. During this year, the group has also contributed to the SEFALER Unit.
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research groups 81