Neurosciences

BBRC

BBRC
Barcelonaβeta Brain Research Center (BBRC), Spain


PROJECT LEADER

Arcadi Navarro, Director of Barcelonaβeta Brain Research Center (BBRC)


HOST ORGANIZATION, COUNTRY

Barcelonaβeta Brain Research Center (BBRC), Spain


DESCRIPTION

”la Caixa” Foundation has worked with the Pasqual Maragall Foundation since 2010, providing continuing structural support for the research, innovation and clinical trial activities conducted by Barcelonaβeta Brain Research Center (BBRC).

The BBRC is a research centre dedicated to the prevention of Alzheimer's disease and the study of cognitive functions affected in healthy and pathological ageing. The centre was established in 2012 by the Pasqual Maragall Foundation with the support of Pompeu Fabra University and ”la Caixa” Foundation.

The BBRC’s mission is to contribute innovative solutions to help decipher and prevent biological changes and cognitive dysfunction associated with neurodegenerative diseases which, due to the aging of the world population, constitute a major global challenge. For example, dementia may reach epidemic levels by the 2050, when it is expected that more than 150 million people will be affected if a way of preventing its appearance and development is not found.

Aimed at preventing neurodegenerative diseases and promoting healthy ageing, the BBRC’s activities are concentrated in the Alzheimer’s Prevention Programme. The programme is structured around three research groups that collaborate from the clinical, cognitive and genetic perspective, and in the fields of biological markers and neuroimaging.

The research conducted by the BBRC is based mainly on data obtained from the Alfa Study, an initiative promoted by ”la Caixa” Foundation. The Alfa Study is a pioneering research initiative aided by nearly 3,000 cognitively unimpaired people aged between 45 and 75 years who voluntarily participate in the BBRC’s research. According to the project they are involved in, these volunteers periodically undergo different clinical tests of cognition and neuroimaging and have the chance to participate in preventive clinical trials.

This cooperation by Alfa Study participants enables researchers to detect biomarkers that may be related to the preclinical stage of Alzheimer's disease, which can begin up to 20 years before the onset of the first clinical symptoms. This early information is key to preventing cognitive deterioration and to acquiring a multidisciplinary understanding of the ageing process and the pathophysiology of neurodegeneration.

Main milestones:

  • MARCH 2018: Alterations are detected in the brain structure of people carrying the gene that conveys the highest risk of developing Alzheimer's disease. The first results from the Alfa Study open the door to improving the design of clinical trials.

  • SEPTEMBER 2019: An artificial intelligence algorithm is developed that, based on magnetic resonance images, facilitates the identification of candidates for Alzheimer's prevention studies. The project receives additional support from ”la Caixa” Foundation through the CaixaResearch Validate call for proposals.

  • JANUARY 2020: For the first time anywhere in the world, changes in the cognitive performance and brain structure of people with insomnia are detected. This finding contributes to a better understanding of the pathophysiology of Alzheimer's disease.

  • NOVEMBER 2020: New tau protein markers are discovered that enable the detection of the preclinical stage of Alzheimer's and in this way improve early diagnosis of the disease.

  • APRIL 2021: New benefits of eating oily fish are discovered in people at risk of developing Alzheimer's disease. The research opens up the possibility of improving the design of dietary interventions.

  • JANUARY 2021: Exposure to air pollution is found to be associated with higher levels of Alzheimer's disease biomarkers. More specifically, higher exposure to nitrogen dioxide and particulate matter of less than 2.5 microns (PM2.5) is associated with increased levels of beta-amyloid protein deposition in the brain, one of the biological alterations that occur in Alzheimer's disease.


TYPE OF SUPPORT

Continued support


MORE INFORMATION

Access all the information through the Barcelonaβeta website

Bilateral agreements

  • Barcelona Brain Health Initiative (BBHI)
    Guttmann Institute

    The goal of the Barcelona Brain Health Initiative (BBHI), a project led by the Guttmann Institute, is to identify indicators that can help to evaluate the state of brain health in individuals so as to indicate what strategies, habits and lifestyles are the most favourable for promoting good brain health throughout life.

    The goal of the Barcelona Brain Health Initiative (BBHI), a project led by the Guttmann Institute, is to identify indicators that can help to evaluate the state of brain health in individuals so as to indicate what strategies, habits and lifestyles are the most favourable for promoting good brain health throughout life.

    To develop this project, more than 5,000 healthy volunteers aged between 40 and 65 years – a suitable age range for the prevention of brain disorders that can appear in later life – take part, providing information about their habits and health indicators.

    A subgroup of more than 1,000 of these volunteers have agreed to take part in a more in-depth study that includes neuropsychological, electrophysiological and medical imaging analyses. Based on the data obtained, the study is aimed at increasing our understanding of the mechanisms that help to maintain the health of our brains throughout life, including such considerations as physical exercise, nutrition, socialisation, cognitive training and sleep.

    In this way, the initiative launched by the BBHI generates knowledge and tools to maintain the functional capacity of the nervous system throughout life, as well as promoting the healthy ageing of the population, a major challenge for biomedical research in the twenty-first century.

    Project leaders: Álvaro Pascual-Leone and García David Bartrés Faz

    Project duration: 2016-2021

    Grant: €3,000,000


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  • VHIR Migraine Adaptive Brain Center
    Vall d’Hebron Research Institute (VHIR)

    The Migraine Adaptive Brain Center, whose work, led by Doctor Patricia Pozo, is supported by ”la Caixa” Foundation and Vall d’Hebron Research Institute, is a unique, pioneering facility of its kind in Spain. The work of the centre, which is dedicated to studying the brain of patients with migraine, combines clinical research, the provision of care, and training and education.

    Migraine is a brain disease that presents with episodic and recurrent attacks of headache associated with other symptoms (hypersensitivity to light, noise and movement, nausea, impaired cognition and so on). Attacks last between 4 and 72 hours and interfere with everyday activities. During a migraine attack, inflammation of the meninges occurs as a result of the release of inflammatory substances from the trigeminal nerve. Pain – which is the most disabling symptom of migraine – is caused by inflammation of the meninges. This type of headache can occur from once a year to several times a week.

    According to the World Health Organisation (WHO), migraine is the second most disabling neurological pathology worldwide. In Spain, it is estimated to affect 12% of the population, that is to say, 4.5 million people (three women for every man). Migraine is considered to be the sixth most disabling disease of all, due to the years of personal and occupational impairment, suffering and loss of productivity it generates. Its causes are unknown, and its treatments are not very effective.

    The concept behind the new facility, which can provide its services to more than 8,000 people a year, is totally innovative. The Migraine Adaptive Brain Center not only combines care provision with clinical research aimed at learning about migraine and improving the health of those affected by it, but also conducts studies aimed at understanding how the brain enables us to adapt to our environment. As a result, its findings can also be transferred to improve the brain health of the population as a whole.

    Project leader: Patricia Pozo Rosich

    Project duration: 2016-2019

    Grant: €660,000


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  • SJD ADHD Project
    Hospital Vall d’Hebron - Vall d’Hebron Research Institute (VHIR) and Hospital Sant Joan

    Around 15-22% of the Catalan school age population presents neurodevelopmental disorders that can lead to academic underachievement, school failure and the appearance of behavioural alterations in adolescence. Attention deficit disorder with or without hyperactivity (ADHD) and specific learning disorders are among the most frequent neurodevelopmental disorders found. The prevalence of these disorders in Catalonia is similar to that of other Western countries. In countries with good academic results, most of these problems are diagnosed and treated from the beginning of compulsory education; in our country, however, only a minority of schoolchildren who need diagnosis and treatment actually receive it.

    "School failure", understood as the number of pupils that do not successfully complete compulsory secondary education (ESO), is a reality and a central problem in our education system. According to figures published by the Government of Catalonia’s Education Ministry, 16-22% of pupils present school failure (the figure varies according to the schools studied and the emergence of new vocational training opportunities). These percentages are much higher than the European average, which stands at around 4-7% of pupils.

    To these percentages must be added the unjustified and similarly high levels of “underachievement at school”, for which no percentages are given. “Underachievement at school” refers to primary and secondary school pupils with a normal or high IQ who would be expected to perform excellently at school, but who instead have serious difficulties in their studies as regards attention, concentration, language, reading, comprehension of written texts, calculation processes and so on.

    Pupils with poor academic performance frequently present very high levels of anxiety, with associated depressive symptoms, the result of the discomfort they experience due to their inability to understand their academic difficulties. Moreover, family, friends, teachers and society in general see them as unmotivated, idle, lazy, or seeking sensations, etc., so that they also feel misunderstood, unfairly punished or, simply, mistreated, which ultimately results in growing lack of interest in the education system.

    The project goals are:

    • To demonstrate, via a three-year prospective study conducted on a population of compulsory secondary education (ESO) pupils in four townships in central Catalonia, that pupils who finish ESO with undiagnosed neurodevelopmental disorders and without a personalised intervention plan are those that obtain the worst academic results and have the most difficulties in passing ESO, as well as greater cannabis use and more impulsive and disruptive behaviours (aggression and violence against people or urban furniture, accidents due to risky behaviour, unwanted pregnancies, problems with the law, marginalisation, etc.), compared to their peers without psychopathology or with those that, despite presenting neurodevelopmental disorders, have received an appropriate intervention plan.

    • To demonstrate that an accurate diagnosis made during the second semester of the second year of compulsory secondary education, followed by the implementation of an appropriate therapeutic approach in the third and fourth years, can prevent and/or reverse school failure and most of the aforementioned dysfunctional problems.

    Project leader: Miquel Casas

    Project duration: 2005-2022

    Grant: €2,450,000

  • Genetic diagnosis in patients with PROS spectrum disorders
    La Paz University Hospital

    PIK3CA gene-related overgrowth spectrum (PROS) is a group of rare disorders that include macrocephaly-capillary malformation syndrome (MCAP) and CLOVES syndrome, among others. It is usually caused by somatic mutations in the PIK3CA gene, changes which are detected only tissues affected in the patient’s body, which makes diagnosis very complex.

    Clinical manifestations and degree of severity depend on the time during embryonic development that the mutation occurs. The aim of the project is to detect new genes or variants associated with the clinical spectrum of vascular syndromes associated with segmental overgrowth.

    The study will make it possible to obtain a molecular genetic diagnosis for a larger number of affected patients and, therefore, improve their medical monitoring. This, in turn, will make it possible to provide optimal advice on the likelihood of recurrence in future pregnancies (either of the parents or of the patient themselves) and, last but not least, to clearly improve their quality of life. This diagnostic capacity can be transferred immediately to routine clinical care.

    Project leader: Víctor Martínez González

    Project duration: 2019-2022

    Grant: €89,657.34

  • Cell therapy for multiple sclerosis and neuromyelitis optica
    Hospital Clínic de Barcelona, IDIBAPS and Gaem Foundation

    Multiple sclerosis (MS) affects 50,000 people in Spain and 2.5 million worldwide. There are at present no therapies that cure this disease. Those that do exist have numerous side effects and are effective in the early stages, but not in advanced disease.

    MS is a chronic, inflammatory disease of the nervous system that destroys myelin, the protective coating around the nerve fibres. It is the second leading cause of neurological disability in young adults (20-40 years), and affects more women than men. The inflammation that occurs during MS exacerbations can cause transient episodes of physical weakness, sensory changes or impaired vision, but over time MS becomes a degenerative disease, with progressively increasing disability. Symptoms vary from person to person, and the progression is determined by the area of damage.

    Within the framework of the research and innovation project supported by ”la Caixa” Foundation and the GAEM Foundation and coordinated by Pablo Villoslada, head of the IDIBAPS Multiple Sclerosis, Pathogenesis and New Therapies group, and Daniel Benítez, a physician from the Immunotherapy Section of the Hospital Clínic’s Immunology Service (IDIBAPS), it has been demonstrated that cell therapy based on tolerogenic dendritic cells is safe and has no adverse effects in the treatment of patients with MS and neuromyelitis optica. This type of cells, obtained from the patient's own blood, are modified to inhibit the inflammatory response characteristic of these diseases.

    The results of the clinical trial also show that this cell therapy can activate a part of the immune system that is responsible for terminating inflammation, and that, therefore, it may be possible stop the damage that these diseases cause to the brain. Since this first study obtained positive results in terms of safety and efficacy, group proposes to continue the trials into a new Phase 2 study to determine clinical efficacy in the control of MS to prevent the increase in disability.

    Project leaders: Daniel Benítez, Irati Zubizarreta and Pablo Villoslada

    Project duration: 2012-2019

    Grant: €1,325,000


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  • SYLVIUS, computer platform to improve neurosurgical planning and epilepsy treatment outcomes
    Hospital del Mar Medical Research Institute (IMIM)

    The Hospital del Mar Medical Research Institute (IMIM) and Galgo Medical, with the support of ”la Caixa” Foundation, have developed SYLVIUS, a platform that enables surgeons to virtually navigate through the patient's brain to plan and receive support during surgical procedures.

    SYLVIUS is a great breakthrough for preparing for brain tumour interventions and for the treatment of epilepsy, as it will offer the possibility of recording, at the same time, all parts of the brain that carry out basic functions, such as neurofunctionality and language, which is among the most delicate functions.

    The platform enables the optimisation of surgery planning by generating a customised model, integrating different medical images of how the patient’s brain functions are organised, identifying areas of special functional risk and helping the surgeon to design a strategy that includes safe areas for the surgical approach. The model is generated in stereoscopic 3D augmented reality for neuronavigation, enabling the surgeon to use it during surgery on the patient's actual head, reducing the risk of injury and optimising the surgical procedure. Moreover, the platform can also generate a general atlas of brain function and connectivity by integrating models of healthy individuals in order to describe organisational patterns in both healthy individuals and patients who need to map functions such as language or others such as motor, sensory or visual functions.

    Project leader: Gerard Conesa

    Project duration: 2014-2022

    Grant: €2,340,000

  • Study of rare neurometabolic diseases and muscular dystrophies
    Autonomous University of Madrid, Isabel Gemio Foundation

    Many patients with rare diseases still lack a clear diagnosis. This fact makes genetic counselling for families very difficult and slows down the application of more personalised therapies based on the mutations causing the pathology.

    This project focuses on the study of two groups of rare neurometabolic diseases: congenital defects of glycosylation and congenital lactic acidosis. These are rare pathologies that are growing constantly and have low diagnostic success rates, mainly due to their very high clinical heterogeneity, the lack of specific biomarkers and their similarly high gene locus heterogeneity.

    The first goal of the project is the genetic characterisation of these neurometabolic disorders using cutting-edge genomic techniques as an initial step towards the identification of novel targets and therapeutic strategies. Once the diagnosis of these pathologies in undiagnosed patients is completed, the next step will be to optimise and develop pharmacological chaperones aimed at stabilising the deficient enzymes produced by the genetic alterations identified.

    Research into the functional properties of potential drugs will be conducted in the cellular context, using patients’ cells to facilitate their future clinical applicability. Moreover, one of the main difficulties in research into inherited metabolic disorders is the lack of optimal cellular models to enable the study of pathophysiological and therapeutic aspects. The cells most commonly used for these analyses are patient-derived skin fibroblasts which, naturally, cannot mimic the patient's cell phenotype. However, the novelty in this project is the generation of induced pluripotent stem cells (iPSCs) and their differentiation into hepatocytes, brain organoids or neural progenitor cells. These cells will help to obtain better understanding of the pathophysiology of these disorders at cellular level, and will also be very useful as a model for testing the effect of pharmacological chaperones.

    Project leader: Belén Pérez González

    Project duration: 2016-2020

    Grant: €410,000

  • iPS cells as a study tool and model for implementing the CRISPR/Cas system in retinal dystrophies
    Ocular Microsurgery Institute Foundation (IMO)

    Retinal dystrophies (RD) are the leading cause of hereditary blindness in developed countries. They are characterised by progressive degeneration of the photoreceptors and cells of the retinal pigment epithelium. Their heterogeneous nature and the fact that there are no prevalent genes or mutations make diagnosis and treatment of the disease difficult.

    The aim of the project, led by doctors Borja Corcóstegui and Esther Pomares, is to contribute to increasing knowledge of retinal dystrophies to better understand the progression of the disease. Under the study, induced pluripotent stem cells (iPSCs) have been generated from cells of patients with retinal dystrophy caused by different mutations. These cells, made available to the entire scientific community, are used as a model to study the causes of the disease and to design strategies that, in the future, may form the basis of a possible therapy for these patients.

    Project leaders: Borja Corcóstegui and Esther Pomares

    Project duration: 2017-2020

    Grant: €300,000

  • VEASID: Optimisation of the protocol for the production of high-capacity adenoviral vectors and application to specific vectors for Dravet syndrome
    Centre for Applied Medical Research (CIMA), University of Navarra

    The production of high-capacity adenoviral vectors (HC-AdVs) is difficult to adapt to industrial scale for clinical use due to the complexity of the method and the relative inefficiency of some of its components. Since HC-AdVs do not encode any viral genes, these vectors are commonly amplified by co-infection with a helper adenovirus (HV), which provides all the proteins necessary for virus particle formation. Contamination with the HV in the final product is avoided by cleavage of the encapsidation signal in its genome through the action of a recombinase (usually Cre recombinase). However, one of the weak points in the process is the genetic instability caused by chronic exposure to recombinase in the cells that support the production of the vectors (packaging cells). This results in slow and unreliable growth, increasing the duration of the process and reducing its reproducibility.

    To solve this problem, the project proposes the use of dimerisable versions of Cre, in which the catalytic domain of the protein is separated into two independent polypeptides that only restore recombinase function when expressed simultaneously in the same cell. Preliminary data indicate that a cell line expressing one of the polypeptides (293-Cre244) retains optimal growth capacity. Moreover, it also retains the property of inactivating an HV that expresses the complementary polypeptide (Ad-Cre245).

    Accordingly, a new system (HV-NO) based on these components (or their optimised versions) is proposed for the production of HC-AdVs. In their current state, both polypeptides (Cre244 and Cre245) are fused to previously described dimerisation domains that respond to rapamycin. However, we have shown that this drug is not necessary to restore recombinase function. As a result, we are considering evaluating new versions that do not contain the dimerisation domains. This could increase their efficacy (as they are smaller proteins), work in favour of the intellectual property of the product, and avoid dependence on previous technologies (rapamycin-induced dimerisation domains).

    Project leader: Rubén Hernández Alcoceba

    Project duration: 2020-2021

    Grant: €100,000

Selected projects