july, 2021

16jul12:0013:00SEMINAR: Ana Sánchez / Candela Machuca12:00 - 13:00 Event Type :SEMINAR Event TagsSEMINAR

Event Details

12:00 – 12:30 Ana Sánchez

Circulating miRNAs profiling in plasma as biomarkers in Wilson disease

Wilson disease (WD) is an inherited disorder of copper metabolism caused by mutations in ATP7B, encoding for a liver copper-transporting protein. ATP7B dysfunction results in a deficit in biliary copper excretion and a progressive accumulation of this metal in the organism, mainly in liver and brain. As WD is a treatable disorder, to achieve an early definitive diagnosis in patients is required; otherwise, it could become in a poor prognosis condition. In this work, circulating miRNAs profiling in plasma has been accomplished to identify biomarkers that could serve to monitor disease progression in WD patients under chelation therapy. Initially, miRNA-seq was performed in a discovery cohort, identifying 18 miRNAs increased in plasma from patients. Five of them stood out, as they are involved in different aspects of liver disease (steatosis, inflammation and fibrosis), iron and lipids metabolism. Plasma levels of these five miRNAs were assessed by qPCR in samples from the discovery cohort and in an independent validation cohort. In both studies, it was confirmed that three of them were induced in plasma from WD patients and showed strong correlation with biochemical liver function markers. Logistic regression models for each miRNA were developed and exhibited good performance classifying patients with poor outcome factors. Finally, potential of these three miRNAs to be used in clinical follow-up was explored, verifying that increased circulating levels in patients are not eventual findings and are repeated over time.

12:30 – 13:00 Candela Machuca

Cerebellar Purkinje cell model generation based in iPSCs technology for the study of two rare neurodegenerative diseases: ARSACS and PLAN

Patient-derived induced pluripotent stem cells (iPSCs) provide an unprecedented opportunity to recapitulate disease pathogenicity without the need for genetic manipulation and creation of gene targeted animal models. New technologies with iPSCs are being developed to make human neurons and have the potential to improve our understanding underlying mechanisms of neurological diseases and development. Cerebellar atrophy is a condition associated with neurodegenerative diseases such as Charlevoix-Saguenay’s Recessive Spastic Ataxia (ARSACS) and PLA2G6-Associated Neurodegeneration (PLAN). ARSACS is an early onset neurodegenerative disorder caused by mutations in the SACS gene, characterized with atrophy in superior cerebellum. PLAN, a NBIA (Neurodegeneration Brain Iron Accumulation) form due to mutations in PLA2G6, is a neuroaxonal dystrophy, which presents cerebellar ataxia. Our aim was to generate a cerebellar Purkinje cell model that will be used as models to investigate the cerebellar neurodegeneration to achieve a rationale therapy. We have developed a differentiation protocol using fibroblasts reprogrammed using Sendai virus to iPSCs, from ARSACS and PLAN patients. For both patients, we derived cerebellar precursors and mature Purkinje cells from iPSCs. Early and late cerebellar markers are being analyzed by molecular techniques. Moreover, functional comparative and electrophysiology analysis with the model are on-going to get a better characterization to gain and insight into the mechanisms of the diseases.



(Friday) 12:00 - 13:00


Centro de Investigación Príncipe Felipe

Eduardo Primo Yúfera, 3 Valencia Spain


Centro de Investigación Príncipe Felipe Eduardo Primo Yúfera, 3