Paediatric Neurometabolic Disorders: Neural Communication Mechanisms and Personalised Therapies
Research Program
Leaders
Where we are
Institut de Neurociències (UBNeuro) - Universitat de Barcelona
Related websites
SJD Barcelona Children’s Hospital Our group conducts translational research focused on the diagnosis and development of treatments that modulate brain biochemistry and neuronal communication mechanisms in monogenic diseases that alter brain metabolism. This therapeutic approach may prove extremely useful in other paediatric neurological diseases.
The group has been affiliated with the Centre for Biomedical Network Research on Rare Diseases (CIBERER) since 2007, an AGAUR consolidated research group since 2000 (2017 SGR 1308) and a RCSU reference centre since 2013. It founded the Connecting the growing brain network and the international working group on neurotransmitter related disorders, i-NTD. It also coordinates the neurotransmitter study subgroup (NOMPS) within the European Reference Network for metabolic diseases (MetabERN), and is a co-researcher, with a European grant, for the development of a Unified European Registry for Inherited Metabolic Diseases (U-IMD).
Researchers in our group are also members of the European Reference Network on Rare Neurological Diseases (ERN-RND).
Research lines
- Clinical, biochemical and neurobiological characterisation and brain connectivity of genetically-determined neurometabolic diseases. This includes defects in neurotransmission, molecules that modulate neuronal communication (glucose, creatine, metals, lipids, etc.) and new categories of this type of condition (e.g. synaptic vesicle diseases).
- Development of laboratory models to study the pathophysiology of neurotransmission disorders and synaptopathies, e.g., use of iPSC to investigate the effect of TH in Mecp2 mouse models.
- Development of personalised therapies based on the knowledge generated in the previous lines of inquiry (the last two projects to be granted funding (CHALLENGES 2018-2020 and Health Research Fund [FIS] 2019-2021) follow this line of research).
Scientific objectives
- To develop and validate registries and databases to enhance clinical and pathophysiological knowledge of genetically-determined neurometabolic diseases.
- To describe and functionally validate new genes associated with neurometabolic diseases or that alter brain neurotransmission.
- To develop and validate robust laboratory methodologies to further investigate the pathophysiology of these diseases and to develop personalised therapies.
- To describe new phenotypes or clinical or biochemical aspects of these diseases, as well as cell neurobiology.
Area/Field of expertise
The main aim of our group is to study genetically-determined metabolic diseases involving cerebral metabolism and, in particular, those that alter synaptic transmission. Many of these have well-established cerebrospinal fluid (CSF) biomarkers. These include defects in neurotransmission and other molecules governing neuronal communication (glucose, creatine, metals, lipids, etc.). Our group has recently described a new category among these pathologies: synaptic vesicle diseases.
We are a multidisciplinary team of neuropaediatricians, neurobiologists, biochemists, molecular biologists, neuropsychologists, neurophysiologists, physicists, engineers and lab technicians. We work closely with the Metabolic Medicine group led by Dr Artuch and deploy the most advanced biochemical analysis methods, including mass spectroscopy, chromatography, specialised CSF analysis, etc.). We adopt a dual approach to our spirit of inquiry: laboratory-based research (synaptic metabolism lab) and clinical research activities.
Regarding our laboratory accomplishments in recent years, we could mention the introduction of techniques to detect specific CSF proteins or the use of cell electrophysiology for studies relating to neurotransmitter release (amperometry). We are also gaining experience in the development of iPSC as well as other cell models for use in functional and therapeutic studies. Last year we commenced the characterisation of new genetic diseases, not previously described in human pathology, that alter brain neurotransmission causing severe early childhood encephalopathy (Sotsiu et al., Oyarzábal et al., in progress).
In terms of our clinical research, in addition to describing new phenotypes and therapeutic possibilities based on neurotransmission defects, we actively participate in international registries (I-NTD, O-IMD) with European funded projects (CHAFEA: Consumers, Health, Agriculture and Food Executive Agency) advancing the clinical and biochemical knowledge of these diseases. Finally, we are also extremely active in the development of clinical guidelines.
Group members
-
Jefe de Grupo Senior
-
Investigador
-
Alfonso Luis De Oyarzabal Sanz
Investigador post-doc
-
Investigador
-
Investigador
-
Técnico
-
Natalia Alexandra Julià Palacios
Investigador pre-doc
-
Investigador pre-doc
-
Investigador
-
Investigador
-
Investigador
-
Investigador post-doc
-
Investigador
-
Investigador
-
Investigador
-
Investigador pre-doc
-
Ayudante de investigación
-
Investigador pre-doc
-
Ayudante de investigación
-
Técnico
Last Publications
- Paredes-Fuentes AJ, Cesar S, Montero-Sanchez R, Latre C, Genovés-Escarre J, Martorell-Sampol L, Cuadras-Palleja D, Colom H, Pineda M, O'Callaghan-Gordo M, Sarquella-Brugada G, Darling A and Artuch-Iriberri R Plasma idebenone monitoring in Friedreich's ataxia patients during a long-term follow-up BIOMEDICINE & PHARMACOTHERAPY . 143: 112143-112143.
- Kuseyri Hübschmann O, Horvath G, Cortés-Saladelafont E, Yildiz Y, Mastrangelo M, Pons R, Friedman J, Mercimek-Andrews S, Wong SN, Pearson TS, Zafeiriou DI, Kulhánek J, Kurian MA, López-Laso E, Oppebøen M, Kilavuz S, Wassenberg T, Goez H, Scholl-Bürgi S, Porta F, Honzík T, Santer R, Burlina A, Sivri HS, Leuzzi V, Hoffmann GF, Jeltsch K, Hübschmann D, Garbade SF, iNTD Registry Study Group, Garcia-Cazorla A and Opladen T Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines. NATURE COMMUNICATIONS . 12(1): 5529-5529.
- Vidal S, Brandi-Tarrau N, Pacheco-Fernández P, Gerotina E, Blasco-Perez L, Trotta JR, Derdak S, O'Callaghan-Gordo M, Garcia-Cazorla A, Pineda M, Armstrong-Moron J and Rett Working Group Author Correction: The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome. SCIENTIFIC REPORTS . 11(1): 18146-18146.
Projects
- Project name:
- AADC deficiency screening in patients with encephalopathies of unknown origin
- Leader
- MªAngels García Cazorla
- Funding entities:
- PTC Therapeutics, Inc.
- Code
- PCP00303
- Starting - finishing date:
- 2021
- Project name:
- Subvencions per a la contractació de personal investigador en formació (PIF-Salut). Beneficiari: Uliana Musokhranova
- Leader
- MªAngels García Cazorla
- Funding entities:
- Departament de Salut - Generalitat de Catalunya
- Code
- SLT017/20/000199
- Starting - finishing date:
- 2021 - 2024
- Project name:
- Teràpies personalitzades pels trastorns cognitiu-conductuals de les malalties hereditàries del metabolisme en l'edat pediàtrica
- Leader
- MªAngels García Cazorla
- Funding entities:
- Agaur - Agència de Gestió d'Ajuts Universitaris i de Recerca
- Code
- 2020 DI 103
- Starting - finishing date:
- 2021 - 2024
Theses
-
Canvis cognitius i cerebrals associats a una intervenció fonològica intensiva en alumnes amb dificultats lectores
- Institution
- UNIVERSIDAD AUTÓNOMA DE BARCELONA
-
Pronòstic neuropsicològic en pacients pediàtrics amb epilèpsia refractaria lesional focal
- Author
- Palacio Navarro, Andrea
- Institution
- UNIVERSIDAD AUTÓNOMA DE BARCELONA
-
Sistemes de neurotransmissió en transtorns pediàtrics
- Author
- Cortés Saladelafont, Elisenda
- Institution
- UNIVERSIDAD DE BARCELONA
News
-
Researchers discover a new genetic disease of the nervous and cardiac systems
The study, led by Dra. Àngels Garcia-Cazorla (Institut de Recerca Sant Joan de Déu), and scientists from IRSJD, IDIBELL and CIBERER, is published in the prestigious journal 'Acta Neuropathologica'.
-
Institut de Recerca Sant Joan de Déu and ICFO create a joint lab to improve neonatal and paediatric health care
The new joint laboratory will advance the use and development of photonic technologies to understand, diagnose, monitor and treat paediatric diseases.
-
The importance of time in the treatment of Rett Syndrome
The research team led by Dr Àngels García-Cazorla (IRSJD) has broken new ground in improving the treatment of Rett Syndrome. Researchers at the Sant Joan de Déu Research Institute (IRSJD) and the Bellvitge Biomedical Research Institute (IDIBELL) have found that early GABAergic modulation may offer a promising strategy for affected children.