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).
Development of leriglitazone for Rett Syndrome and related disorders
Investigador principal: Àngels García Cazorla
Convocatoria: proyectos colaboración público-privada
Código: CPP2021-008554
Año inicio: 2022
Año finalización: 2025
Financiador: Ministerio de Ciencia e innovación, Agencia Estatal de investigación
Importe concedido: 255.946,00 €
Proyecto CPPC2021-008554 financiado por MICIN/AEI/10.13039/501100011033 y por la Unión Europea NextGenerationEU/PRTR
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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Natalia Alexandra Julià Palacios
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Investigador pre-doc
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Silvia Constancia Liendo Vallejo
Ayudante de investigación
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Ayudante de investigación
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Jennifer Anticona Huaynate
Ayudante de investigación
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Ayudante de investigación
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Ayudante de investigación
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Investigador
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Ayudante de investigación
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Last Publications
- Jana Domínguez Carral, Ludlam WG, Junyent Segarra M, Fornaguera Marti M, Balsells S, Muchart-Lopez J, Cokolic Petrovic D, Espinoza I, Ortigoza-Escobar JD and Martemyanov KA Severity of GNAO1-Related Disorder Correlates with Changes in G-Protein Function. ANNALS OF NEUROLOGY . 94(5): 987-1004.
- Musokhranova U, Grau-Páez C, Vergara C, Rodríguez-Pascau L, Xiol-Viñas C, Castells AA, Alcántara S, Rodríguez-Pombo P, Pizcueta P, Martinell M, Garcia-Cazorla A and De Oyarzabal-Sanz AL Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome. JOURNAL OF TRANSLATIONAL MEDICINE . 21(1): 756-756.
- Stanescu S, Correcher Medina P, Del Castillo FJ, Alonso Luengo O, Arto Millan LM, Belanger Quintana A, Camprodon Gomez M, Diez Langhetée L, Garcia Campos O, Matas Garcia A, Perez-Moreno J, Rubio Gribble B, Visa-Reñé N, Giraldo-Castellano P and O'Callaghan-Gordo M Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study. Biomedicines . 11(10): .
Projects
- Project name:
- Enfermedad es Bpan
- Leader
- Alejandra Darling , Alfonso Luis De Oyarzabal Sanz
- Funding entities:
- ZZZZ_O.H.S.J.D.-Curia Provincial, Provincia San Juan de Dios de España
- Code
- PFNR0186
- Starting - finishing date:
- 2023
- Project name:
- Eficacia y tolerabilidad de la coenzima Q (Ubiquinol) en pacientes con trastornos mitocondriales y ataxias cerebelosas
- Leader
- MªAngels García Cazorla
- Funding entities:
- Instituto de Salud Carlos III (ISCIII)
- Code
- ICI22/00092
- Starting - finishing date:
- 2023 - 2026
- Project name:
- Entrega de MeCP2 en el cerebro mediante el uso de nanocápsulas para el tratamiento del síndrome de Rett
- Leader
- Alfonso Luis De Oyarzabal Sanz
- Funding entities:
- Generalitat de Catalunya
- Code
- SLT033/23/000097
- Starting - finishing date:
- 2023 - 2024
Theses
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Comprehensive analysis of diagnostic approaches and molecular landscape of Rett syndrome spectrum disorders
- Author
- Xiol Viñas, Clara
- Institution
- UNIVERSIDAD DE BARCELONA
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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
News
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The amino acid L-serine shows efficacy in treating patients with mutations in GRIN genes
A clinical trial led by Dr Àngels García-Cazorla (IRSJD), has demonstrated the potential of the amino acid L-serine, administered as an oral supplement, to improve the function of glutamate receptors in patients with GRINpathies. The trial involved 24 children from different hospitals in Spain.
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Nanomedicine to tackle rare diseases
Experts in nanomedicine from various fields have gathered today for the fifth consecutive year at Nano Rare Diseases Day. This event is co-organized by IRSJD and the NANOMED Spain platform, coordinated by IBEC.
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Advances in Research on Rett Syndrome
A study conducted by the Paediatric Neurometabolic Disorders: Neural Communication Mechanisms and Personalised Therapies Group at IRSJD · SJD Barcelona Children's Hospital confirms mitochondrial dysfunction in two distinct models of Rett syndrome, highlighting the significance of distinguishing between brain regions and stages of the disease. The findings of this study open up new avenues for treatment development.