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Inherited Metabolic Medicine
Scientific Programmes
In 2015 the 12 groups forming the Programme obtained relevant scientific results and got a large number of strategic actions under way to tackle RD whose main aspect is the alteration of home- ostasis caused by mutations in genes connected with intermediary metabolism.
First of all, we have the results on new genes and applications for better diagnosis of this group of diseases. We could stress the discovery of mu- tations in the ALDH18A1 gene which cause dom- inant or recessive inherited diseases depending on the lesion of the gene, work done by Dr. Rubio’s group (U739).
The identification by Dr Ribes’s group (U737) of a new biomarker (Cholestane-3ß,5a, 6ß-triol) for Niemann-Pick type C disease, Cerebrotendine- ous xanthomatosis and lysosomal acid lipase deficiency and the implementation by Dr Giraldo’s group (U752) of enzymatic determination in dried blood spots for screening lysosomal acid lipase (LAL) deficit and the Chitotriosidase biomarker.
There has also been cooperative work between several units in the Programme to prepare guides and recommendations for improving the neonatal screening of homocystinurias and methylmalonic aciduria, in the group “Newborn screening work- ing group” in the framework of European project E-HOD (European Network and Registry for Ho- mocystinurias and Methylation Disorders).
The programme has developed new models of disease to find out the physiopathological bas- es of these diseases. For example, Dr. Grinberg’s group (U720) has completed a neuronal model by means of iPS cells for Sanfilippo C disease and successfully carried out fibroblast treatment us- ing RNA interference. Dr Palacín’s group (U731) has, in cooperation with Dr. Artuch (U703), made progress in phenotyping the first animal model of lysinuric protein intolerance (LPI).
As regards the progress made in molecular as- pects of these diseases, we should stress the determination of the structure of human CPS1 whose deficiencies produce congenital hyperam- monaemia and the characterisation of the effects of clinical mutations of the CPS1-regulating do- main by Dr. Rubio’s group (U739). In the context of MLC disease Dr Estévez’s group (U750), in co- operation with unit (U730) under Dr Nunes, have taken steps forward in the understanding of the structure-function relationship of GlialCAM and the modulation of the functional properties of the ClC-2 chloride channel.
Lastly, we would like to stress the achievements in the therapeutic and clinical aspects of these diseases such as the identification of new thera- peutic targets as controllers of mitochondrial bio- genesis (Sirt1/PGC-1/PPAR axis) and the autoph- ageal flow (via mTOR) in adrenoleukodystrophy (Dr Pujol U759), or the study of Dr Salido’s group (U740) on the safety and effectiveness of the re- duction of substrate in primary hyperoxalurias by glycolate oxidase inhibition with two approaches; siRNA and small molecules.
CIBERER I Annual report 2015 I 19