Page 41 - CIBERER-2015-eng

Most relevant scientific articles
Research Groups
camara Y, carreño-gago l, martín ma, melià mJ, BláZqueZ a, delmiro a, et al. Severe TK2 enzyme activity deficiency in patients with mild forms of myopathy. Neu- rology. 2015;In press.
halter J, schuPBach Wm, casali c, elhasid r, FaY K, hammans s, et al. Allogeneic hematopoietic SCT as treat- ment option for patients with mitochondrial neurogastro- intestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant. 2011 Mar;46(3):330-7.
Brull a, de luna n, Blanco-grau a, lucia a, martin ma, arenas J, et al. Phenotype consequences of myophos-
Highlights
During 2015 our group has achieved important sci- entific goals on the field of mitochondrial genetics, mtDNA replication defects and McArdle disease. We have made a significant advance towards bringing our research from bench to bedside.
In the field of mitochondrial genetics we have estab- lished a coordinated strategy to identify the molec- ular and genetic causes of the diseases of the mito- chondrial OXPHOS system integrating genetic and genomic methods.
Regarding the mtDNA replication defects, we have continued our pre-clinical studies on deoxyribonu- cleoside administration using cell and mouse mod- els (TK2 knockout mouse donated by Dr. Karlsson, Karolinska Institutet, Stcokholm, Sweden). We have also strengthened our interaction with physicians and patient associations. Due to this interaction we have contributed broadening the clinical spectrum of TK2 mutations. We have recently obtained im- portant results indicating that deoxyribonucleoside supply may be effective for many other mtDNA rep- lication defects. This resulted in a registered patent at the European and American agencies. Our collab- orative project including pre-clinical studies and the follow-up of patients undergoing compassionate treatment has been awarded by ISCIII (Personalized Medicine Call).
phorylase dysfunction: insights from the McArdle mouse model. J Physiol. 2015 Jun 15;593(12):2693-706.
de luna n, Brull a, guiu Jm, lucia a, martin ma, arenas J, et al. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro. Dis Model Mech. 2015 May;8(5):467-72.
nogales-gadea g, Brull a, santalla a, andreu al, are- nas J, martin ma, et al. McArdle Disease: Update of Re- ported Mutations and Polymorphisms in the PYGM Gene. Hum Mutat. 2015 Jul;36(7):669-78.
We have also continued our work on gene therapy for MNGIE by developing vectors that drive thymi- dine phosphorylase expression and ensure the safe- ty and efficiency requirements. We have consolidat- ed an international consortium aimed to conduct a clinical trial using our orphan-drug designated AAV and coordinated a proposal to the H2020 call with this goal.
Concerning McArdle disease we have continued the characterization of the knockin murine mod- el. We have found that the main enzymes involved in glycogen metabolism are distinctly affected in metabolically different types of muscle (glycolytic versus oxidative). Additionally, we have evaluated the efficacy of valproic acid (VPA) as a treatment for McArdle disease. Finally, we have consolidated our collaboration with the Neuromuscular Research Unit, Rigshospitalet (Copenhagen, Denmark), to understand the physiopathologic mechanisms in- volved in the disease.
Institution: Fundación Hospital Universitario Vall d’Hebron - Institut de Recerca (VHIR)
Contact: Hospital Vall d’Hebron. Passeig Vall d’Hebron, 119-129. 08035 Barcelona
Tel.: 93 489 40 54 · E.mail: [email protected]
Website: http://www.vhir.org/portal1/grup-presentacio.asp?s=recerca&contentid=9223&idrefer=9071
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