Grants for Scientific Research Teams in Biomedicine
The BBVA Foundation funds the work of front-line teams in critical health areas like oncology, cardiology and neurodegenerative disease
· The BBVA Foundation Grants for Scientific Research Teams in the Biomedicine area have been awarded to five teams from out of 324 submitting projects in the second call
· The five teams, comprising a total of 35 investigators, will each receive 150,000 euros and will have three years in which to carry out their projects
· The grants are decided in an independent, competitive process by evaluation committees formed by experts in each area
· Awardee teams are pursuing new treatment avenues in Alzheimer’s and Parkinson’s and in glioblastoma, among the most aggressive types of cancer. They seek to achieve a deeper understanding of tumors and their relationship with low oxygen levels in cells and to penetrate the genetic origin of the common heart condition known as atrial fibrillation
Madrid, October 8, 2015.- The BBVA Foundation has centered its 2015 Grants for Scientific Research Teams in Biomedicine on cardiology, oncology and neurodegenerative diseases, three sets of conditions that pose serious challenges to biomedical knowledge and the care of health, due to their high prevalence and broad social and sanitary impact.
The grants are directed at research groups in public or private universities, and other non-profit institutions headquartered in Spain engaging substantially in research, that submit highly innovative projects of a basic, translational or applied nature.
On this occasion, the committee has selected five research teams with a total of 35 members. All projects, even those involving basic research, have clear translational potential, since understanding the mechanisms of a disease is a first step to identifying biomarkers for its early detection or developing therapeutic advances. Specifically, the teams funded in the present edition are pursuing new treatment paths for Alzheimer’s and Parkinson’s disease and for glioblastoma, a particularly invasive type of cancer; they seek to achieve a deeper understanding of the link between poor cell oxygenation and cancer, and to penetrate the genetic origin of the common heart condition known as atrial fibrillation.
Each team will receive a grant of up to 150,000 euros with three years in which to carry out their project. Innovativeness, the nature of the advance being targeted and its application to diagnosis, treatment and/or prevention are among the key criteria against which candidates are appraised.
The five recipients were chosen out of new fewer than 324 top-level teams summing 2,320 investigators. Evaluation is initially undertaken by three committees formed by leading experts in the areas addressed: oncology, cardiology and neurodegenerative diseases. A final general committee drawing members from each then ratifies their choices.
Award of BBVA Foundation Grants for Research Teams in Biomedicine
The evaluation committee, whose membership appears below, has resolved to award the five grants envisaged in the call to the following principal investigators and projects:
Project: The Immortalization and Hypoxia Connection, Contribution in Cancer
Principal investigator: Amancio Carnero, researcher at the Instituto de Biomedicina de Sevilla (IBIS/CSIC).
Project: Neuroprotection in Parkinson’s Disease: A Potential Therapy Based on Stimulation of Endogenous GDNF Production
Principal investigator: Xavier D’Anglemont de Tassigny, Miguel Servet Investigator at the Instituto de Biomedicina de Sevilla (IBIS/CSIC), Hospital Universitario Virgen del Rocío.
Project: Nanoparticle-Based, Brain-Exclusive Delivery of p38MAPK Inhibitors for the Treatment of Alzheimer’s Disease
Principal investigator: Carlos Dotti, research professor at the Centro de Biología Molecular Severo Ochoa (CSIC-UAM). Madrid.
Project: Validation of an Innovative Anti-Myc Therapy in Glioblastoma
Principal investigator: Laura Soucek, research professor at Vall d’Hebron Instituto de Oncología (VHIO).
Project: Role of the Cardiac Pacemaker Channel (HCN4) in Early-Onset Familial Atrial Fibrillation (a New Mechanism in the Genesis and Maintenance of Atrial Fibrillation)
Principal investigator: Juan Tamargo Menéndez, Professor of Pharmacology in the School of Medicine of the Universidad Complutense de Madrid.
Description of selected projects
PROJECT: The Immortalization and Hypoxia Connection, Contribution in Cancer
Principal investigator: Amancio Carnero, researcher at the Instituto de Biomedicina de Sevilla (IBIS/CSIC)
Team members:
Juan José Marín López, PhD assistant professor, School of Medicine, University of Seville.
José Manuel García Heredia, PhD assistant professor, School of Biology, University of Seville.
Sandra Muñoz Galván, Juan de la Cierva Postdoctoral Investigator, Instituto de Biomedicina de Sevilla.
Marco Pérez, research biologist, Instituto de Biomedicina de Sevilla.
Felipe Abrio Blanca, FPU intern, Instituto de Biomedicina de Sevilla.
Eva María Verdugo Sivianes, master’s student, Instituto de Biomedicina de Sevilla.
Manuel Pedro Jiménez-García, predoctoral student, Instituto de Biomedicina de Sevilla.
Purificación Estévez García, physician in the Clinical Oncology Department, Hospital Universitario Virgen del Rocío, Seville.
Project description:
The team led by Amancio Carnero has spent years investigating cell senescence, the normal process of cell aging and death. This process is a first line of defense against the development of tumors; indeed cancer cells are characterized by the disappearance of this control mechanism, triggering runaway growth.
In this project funded by the BBVA Foundation, the team will analyze hypoxia, i.e., the oxygen deprivation that is a widespread feature of solid tumors. The goal is to ascertain – first in tissue samples then in laboratory animals – whether hypoxia contributes to eliminating cell senescence, causing cell immortality and by this means favoring the appearance or progression of tumors.
Further, a series of chronic conditions are characterized by hypoxia or depleted oxygen levels; for instance, smoking-related chronic obstructive pulmonary disease. The research team will reproduce these conditions in the lab and in animals to examine whether low oxygen increases the risk of developing cancer in response to environmental carcinogens (tobacco for example).
Although this is basic research, it holds out medium- and long-term clinical potential. As Carnero explains, “in attempting to confirm the hypothesis that hypoxia increases cancer risk by blocking cell senescence, we may come across genetic biomarkers that indicate which sufferers of these respiratory diseases are most at risk of developing a tumor, thereby facilitating early diagnosis. These biomarkers could indicate, for instance, how individual patients might respond to treatment, allowing us to fine tune the therapeutic approach. There is also a chance that increasing oxygen supply could boost patients’ therapeutic response through its effect on the tumor microenvironment.”
PROJECT: Neuroprotection in Parkinson’s Disease: A Potential Therapy Based on Stimulation of Endogenous GDNF Production
Principal investigator: Xavier D'Anglemont de Tassigny. Miguel Servet Investigator at the Instituto de Biomedicina de Sevilla (IBIS/CSIC), Hospital Universitario Virgen del Rocío.
Team members:
Daniel Enterría-Morales, doctoral student, University of Seville.
Ivette López-López, technician, University of Seville.
Project description:
This project will explore a new therapeutic strategy against Parkinson’s disease based on stimulating the GDNF protein produced naturally in the brain.
Parkinson’s disease, which affects 1% of the over-60s population, causes severe impairment of patients’ mobility and cognitive functions. Its origin lies in the death of a specific neuronal population known as dopaminergic neurons, a process which no current treatment deals with efficiently. The project takes as its starting point the existence of a protein, neurotrophic factor GDNF, with the ability to prolong the survival of dopaminergic neurons. To date, its therapeutic use has been hindered by the fact that GDNF cannot cross the blood-brain barrier protecting the cerebral tissue.
It has recently been discovered that GDNF is synthesized in the brain albeit at very low levels. The goal of this project is to find a way to boost GDNF production in the brain as a means to protect dopaminergic neurons. If the results are positive, they could rapidly be translated to the treatment of Parkinson’s disease.
PROJECT: Nanoparticle-Based, Brain-Exclusive Delivery of p38MAPK Inhibitors for the Treatment of Alzheimer’s Disease
Principal investigator: Carlos Dotti, research professor at the Centro de Biología Molecular Severo Ochoa (CSIC-UAM).
Team members:
José Antonio Esteban García, research professor, Centro de Biología Molecular Severo Ochoa (CSIC-UAM).
Ángel Rodríguez Nebreda, ICREA Professor, IRB Barcelona.
Jesús Martínez de la Fuente, researcher, Instituto de Ciencias de Materiales Aragón.
Sandra Colié, postdoctoral researcher, IRB Barcelona.
Adrián Martín Segura, research technician, Centro de Biología Molecular Severo Ochoa (CSIC-UAM)
Irene Palomares Pérez, research technician, Centro de Biología Molecular Severo Ochoa (CSIC-UAM)
Marta Navarrete Llinás, postdoctoral researcher, Centro de Biología Molecular Severo Ochoa (CSIC-UAM).
Laura De Matteis, researcher at the Instituto de Nanociencia de Aragón (INA), University of Zaragoza.
Project description:
Carlos Dotti’s research focuses on why ageing is accompanied by loss of memory and of learning capacity, a line of work which may shed light on the causes of Alzheimer’s disease. This project, specifically, explores a possible therapeutic strategy in Alzheimer’s based on the enzyme known as p38MAPK, which is implicated in inflammation.
Many experiments in laboratory animals have found a direct link between a marked inflammatory response in the brain and the subsequent appearance of Alzheimer’s. However, clinical trials with conventional anti-inflammatories have failed to demonstrate a decisive role for inflammation in the disease in humans. This may be because clinical trials involved patients with already irreversible brain alterations and perhaps because trails employed anti-inflammatory drugs targeting a single inflammation pathway other than the pathway used by p38MAPK.
The project, accordingly, will focus on the p38MAPK enzyme, particularly at compounds directed at inhibiting its activity. The p38MAPK inhibitors already available on the market induce numerous and severe side effects because they also block the enzyme where it is needed, especially in the liver. The solution proposed comprises a new pharmaceutical formulation and a nasal administration route, so inhibitor activity is confined solely to the brain.
The team will use a new Alzheimer’s animal model in which biochemical changes, as in humans, precede the cognitive symptoms of the disease. The results will allow to determine whether brain-only p38MAPK inhibition may be a therapeutic alternative in Alzheimer’s, above all at early stages when cognitive impairment is still relatively mild.
PROJECT: Validation of an Innovative Anti-Myc Therapy in Glioblastoma
Principal investigator: Laura Soucek, research professor at Vall d’Hebron Instituto de Oncología (VHIO).
Team members:
Jonathan Richard Whitfield, staff scientist, Vall d'Hebron Institutode Oncología.
Marie-Eve Beaulieu, postdoctoral researcher, Vall d'Hebron Institutode Oncología.
Daniel Massó Vallés, doctoral student, Vall d'Hebron Institutode Oncología.
Toni Jauset González, doctoral student, Vall d'Hebron Institutode Oncología.
Erika Serrano del Pozo, laboratory technician, Vall d'Hebron Institutode Oncología.
Sandra Martínez, predoctoral student, Vall d'Hebron Institutode Oncología.
Project description:
This project sets out to preclinically validate (in laboratory animals) a peptide with therapeutic potential in glioblastoma as an intranasal drug.
Glioblastoma, the most common form of brain tumor, is almost invariably lethal and has no effective treatment. Much research attention in oncology has been drawn towards the Myc protein. This protein is vital in the expression of up to 15% of human genes and its alteration triggers the uncontrolled cell proliferation that is characteristic of cancer processes. In fact, Myc is deregulated in most human tumors in sites like the cervix, breast, colon, lung, pancreas, stomach and brain.
The group led by Laura Soucek has designed Omomyc, a Myc inhibitor shown to have a dramatic therapeutic impact in glioblastoma (in animal models) by hindering the replication of tumor cells, leading to their death.
Omomyc has so far been considered a proof of principle with applications confined to gene therapy, putting difficulties in the way of its translation to the clinic.
The team, however, has found that the Omomyc peptide has the ability to penetrate the cell wall, opening up the possibility of its direct pharmaceutical administration. The fact that it is capable of crossing the blood-brain barrier, the structure that protects the brain from toxins and infections but also blocks the passage of many drugs, should facilitate intranasal delivery and thereby its application in glioblastoma.
The team will validate Omomyc therapeutically in mouse models by transplanting tumors from human patients with glioblastoma, in a bid to translate the promising results obtained in gene therapy to a viable therapeutic option.
PROJECT: Role of the Cardiac Pacemaker Channel (HCN4) in Early-Onset Familial Atrial Fibrillation (a New Mechanism in the Genesis and Maintenance of Atrial Fibrillation)
Principal investigator: Juan Tamargo Menéndez, Professor of Pharmacology in the School of Medicine of the Universidad Complutense de Madrid.
Team members:
María Eva Delpón Mosquera, professor, Department of Pharmacology, Universidad Complutense de Madrid.
Ricardo Caballero Collado, associate professor, Department of Pharmacology, Universidad Complutense de Madrid.
Ricardo Gómez García, researcher, Department of Pharmacology, Universidad Complutense de Madrid.
Adriana Barana Muñoz, researcher, Department of Pharmacology, Universidad Complutense de Madrid.
Irene Amorós García, researcher, Department of Pharmacology, Universidad Complutense de Madrid.
Marta Pérez-Hernández Durán, predoctoral researcher, Department of Pharmacology, Universidad Complutense de Madrid.
Marcos Matamoros Campos, predoctoral researcher, Department of Pharmacology, Universidad Complutense de Madrid.
Project description:
The project team will seek to identify the mechanism whereby mutations in the cardiac channel (HCN4) controlling pacemaker activity lead to familiar atrial fibrillation, with the hope of identifying new treatment targets.
Atrial fibrillation is the most frequently diagnosed cardiac arrhythmia, affecting 900,000 people in Spain. It is also responsible for 20% of strokes, a cerebrovascular pathology that is the first cause of death in women and the second in men. Treatment efficacy, however, is constrained by a lack of understanding of the mechanisms behind its appearance and progression.
The team at the Universidad Complutense forms part of the ITACA Consortium, which has studied three generations of a family (54 members) presenting atrial fibrillation unaccompanied by with other cardiovascular or electrophysiological disorders, making them ideal subjects to determine which alterations are unique to the disease.
In the course of these studies, four members of the second generation were found to have a new mutation in the HCN4 channel responsible for the automatic activity of the pulmonary veins. The BBVA Foundation funded project will permit completion of the genetic testing of family members, alongside in vitro analysis of the mutation’s functional consequences and interaction with other channels. The team will also examine its effects on ion currents and electrical impulse conduction in heart cells differentiated from human induced pluripotent stem cells, and develop a transgenic mouse that carries the mutation.