Page 36 - CIBERER-2015-eng

Platforms
PROTEOmAb
The aim of this platform is to transfer metabolism to the field of RD for identifying new pathology bio- markers and possible therapeutic targets. Quanti- tative methods are applied for the assessment of the expression of enzymes controlling metabolic activities using the technology of reverse phase protein microarrays. The procedure involves an- tibodies validated against glycolytic enzymes,
• Peripheral neuropathies. In the framework of the TREAT-CMT project and in cooperation with units U732 and U763 it has been iden- tified in skin biopsies of patients with Char- cot-Marie-Tooth (CMT) 1A that proteins of the OXPHOS system, of the antioxidant system and of the β-oxidation provide new biomarkers for progression of the disease (Plasma-me-
the pentose phosphate cycle, decarboxylation of pyruvate, Krebs cycle, β-oxidation, shuttles, the electron transport chain, oxidative phosphoryla- tion, mitochondrial structure and dynamics, anti- oxidant system, etc.
The milestones reached this year focus on three activities:
IDENTIFICATION OF NEW DIAGNOSIS BIOMARK- ERS AND PROGRESS OF THE PATHOLOGY IN BIOPSIES OF PATIENTS AFFECTED BY RD.
• Myopathies: In cooperation with unit U723 new diagnosis biomarkers have been iden- tified in Duchenne (DMD) and Becker (BMD) muscular dystrophies, carriers of DMD and BMD (Xp21 carriers), type 2 C hip dystrophy (LGMD2C), neuronal ceroid lipofuscinosis (NCL), type V glycogenosis (McArdle), myo- pathies through complex I deficiencies or by admittance to the intensive care unit (Jour- nal of Translational Medicine 2015 Feb 18; 13:65). The corresponding patent (2432653) owned by CIBERER/UAM was granted on 10/09/2015.
tabolite and skin-protein signatures of Char- cot-Marie-Tooth 1 A provide novel biomark- ers of disease. Soldevilla B, Cuevas-Martín C, Ibáñez C, Al- berti MA, Simó C, Santacatterina F, Casasno- vas C., Márquez C, Sevilla T, Pas- cual S, Sán- chez-Aragó M, Espinós C, Palau F and Cuezva JM. (submitted) (2016).
PHENOTYPING OF ANIMAL MODELS OF RD.
In cooperation with unit U732 an analysis has been made of the metabolic phenotype of the different tissues of the knockout mouse for gene Gdap1, which is a murine model of CMT disease. It has been verified that the expression of proteins of glycolysis, OXPHOS and of mitochondrial dynam- ics are specifically reduced in peripheral nerves (PLoS Genetics, 2015 Apr 10;11(4):e1005115).
IDENTIFICATION OF BIOMARKERS OF RESPONSE TO THERAPY IN MODELS OF RD.
In cooperation with unit U755 an analysis of the phenotype of the mouse model of human reti- nitis pigmentosa (rd10) and of the response to treatment by the Adalimumab antibody has been made, identifying metabolic markers of thera- peutic response preventing the death of photore- ceptors (Scientific Reports, 2015 Jul 14; 5:11764).
36 I Annual report 2015 I CIBERER