Research Neuroscience

Paediatric Neurometabolic Disorders: Neural Communication Mechanisms and Personalised Therapies

Research Program

Neuroscience

Leaders

Where we are

Institut de Neurociències (UBNeuro) - Universitat de Barcelona

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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

  1. 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).
  2. 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.
  3. 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

  1. To develop and validate registries and databases to enhance clinical and pathophysiological knowledge of genetically-determined neurometabolic diseases.
  2. To describe and functionally validate new genes associated with neurometabolic diseases or that alter brain neurotransmission.
  3. To develop and validate robust laboratory methodologies to further investigate the pathophysiology of these diseases and to develop personalised therapies.
  4. 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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Projects

Project name:
Modelos experimentales de sinaptopatías aplicados a la medicina personalizada de trastornos genéticos raros de la comunicación neuronal neuropediátricos
Leader
MªAngels García Cazorla, Alfonso Luis De Oyarzabal Sanz
Funding entities:
Instituto de Salud Carlos III (ISCIII)
Code
PI24/00469
Starting - finishing date:
2024 - 2027
Project name:
Una aproximación multifactorial para avanzar en el estudio de las terapias para enfermedades mitocondriales neurodegenerativas, utilizando COXPD1 como modelo
Leader
Alejandra Darling
Funding entities:
Fundació Institut de Recerca Biomèdica (IRBB)
Code
PCP00427
Starting - finishing date:
2024 - 2025
Project name:
Enfermedades Neurodegenerativas de inicio en la infancia de origen genético: identificación y caracterización de entidades asociadas a la autofagia
Leader
Alejandra Darling
Funding entities:
Asociacion Bpan Spain
Code
PCP00418
Starting - finishing date:
2024 - 2025
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Theses

  • Comprehensive analysis of diagnostic approaches and molecular landscape of Rett syndrome spectrum disorders
    Author
    Xiol Viñas, Clara
    Institution
    UNIVERSIDAD DE BARCELONA
    22/12/2023
  • Canvis cognitius i cerebrals associats a una intervenció fonològica intensiva en alumnes amb dificultats lectores
    Institution
    UNIVERSIDAD AUTÓNOMA DE BARCELONA
    07/10/2020
  • Pronòstic neuropsicològic en pacients pediàtrics amb epilèpsia refractaria lesional focal
    Author
    Palacio Navarro, Andrea
    Institution
    UNIVERSIDAD AUTÓNOMA DE BARCELONA
    29/09/2020
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