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
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Jefe de Grupo Senior
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Alfonso Luis De Oyarzabal Sanz
Investigador post-doc
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Investigador
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Investigador
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Técnico
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Natalia Alexandra Julià Palacios
Investigador pre-doc
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Investigador pre-doc
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Investigador
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Investigador
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Investigador
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Investigador
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Ayudante de investigación
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Investigador pre-doc
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Técnico
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Silvia Constancia Liendo Vallejo
Ayudante de investigación
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Ayudante de investigación
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Ayudante de investigación
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Ayudante de investigación
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Jennifer Anticona Huaynate
Ayudante de investigación
Last Publications
- Luque J, Mendes I, Gómez B, Morte B, de Heredia ML, Herreras E, Corrochano V, Bueren J, Gallano P, Artuch-Iriberri R, Fillat C, Pérez-Jurado LA, Montoliu L, Carracedo Á, Millán JM, Webb SM, Palau F, CIBERER Network and Lapunzina P CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative. CLINICAL GENETICS . 101(5-6): 481-493.
- Casas-Alba D, Darling A, Caballero E, Mensa-Vilaró A, Bartrons J, Anton-Lopez J, Garcia-Cazorla A, Vanderver A and Armangue-Salvador T Efficacy of baricitinib on chronic pericardial effusion in a patient with Aicardi-Goutières syndrome. Rheumatology . 61(4): 87-89.
- Aparicio J, Niñerola-Baizán A, Perissinotti A, Rubí S, Muchart-Lopez J, Candela-Cantó S, Campistol-Plana J and Setoain X Presurgical evaluation of drug-resistant paediatric focal epilepsy with PISCOM compared to SISCOM and FDG-PET. SEIZURE-EUROPEAN JOURNAL OF EPILEPSY . 97: 43-49.
Projects
- Project name:
- Sinapsis en un chip: medicina personalizada en trastornos genéticos del neurodesarrollo que afectan a la comunicación sináptica
- Leader
- MªAngels García Cazorla
- Funding entities:
- Instituto de Salud Carlos III (ISCIII)
- Code
- PI21/00073
- Starting - finishing date:
- 2022 - 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
- Project name:
- TREAT-AHC. Identification of compounds for the treatment of Alternating Hemiplegia of Childhood by drug repositioning. Molecular and pre-clinical evaluation and clinical outcome measure validation
- Leader
- Maria del Carmen Fons Estupiña
- Funding entities:
- Fundació La Marató de TV3
- Code
- 283/C/2020
- Starting - finishing date:
- 2021 - 2024
Theses
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Canvis cognitius i cerebrals associats a una intervenció fonològica intensiva en alumnes amb dificultats lectores
- Institution
- UNIVERSIDAD AUTÓNOMA DE BARCELONA
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Pronòstic neuropsicològic en pacients pediàtrics amb epilèpsia refractaria lesional focal
- Author
- Palacio Navarro, Andrea
- Institution
- UNIVERSIDAD AUTÓNOMA DE BARCELONA
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Sistemes de neurotransmissió en transtorns pediàtrics
- Author
- Cortés Saladelafont, Elisenda
- Institution
- UNIVERSIDAD DE BARCELONA
News
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Supplementation with dopamine and serotonin precursors could have neuroprotective effects in children with early-onset epilepsy
A team of researchers at the Institut de Recerca Sant Joan de Déu shows that supplementation with neurotransmitters such as dopamine and serotonin could protect the brains of children under the age of 3 with early-onset epilepsy. The article was published in the scientific journal Developmental Medicine & Child Neurology.
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Researchers discover new phenotypic characteristics in inherited disorders of neurotransmitter metabolism
The study co-led by Dr Àngels Garcia-Cazorla, Institut de Recerca Sant Joan de Déu (IRSJD), has studied more than 270 patients with ultra-rare neuro-metabolic diseases to describe and evaluate their initial clinical and biochemical characteristics improve their diagnosis.
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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'.