Researchers at the Biomedical Research Institute Sant Pau (IIB Sant Pau) of the Hospital de la Santa Creu i Sant Pau, together with researchers at the Universitat Autònoma de Barcelona (UAB), the Spanish Scientific Research Council (CSIC) and the Network for Biomedical Research in the Bioengineering, Biomaterials and Nanomedicine Network (CIBER-BBN), have published an article in one of the most prestigious international scientific journals in the field of Molecular Medicine, EMBO Molecular Medicine. This article demonstrates the efficacy of a nanopharmaceutical developed by this team that selectively eliminates metastatic stem cells in animal models of colon cancer.

The research team, led by Dr Ramon Mangues (IIB Sant Pau), Prof Antonio Villaverde (UAB) and Dr Esther Vázquez (UAB), all members of the CIBER-BBN, have demonstrated that the drug acts only on metastasis initiating cells, through the specific interaction between a peptide present in the protein nanoparticle that transports it and the cellular receptor CXCR4 that is overexpressed in tumour cells. This allows targeting only tumour cells, to block their dissemination at early cancer stages, by preventing the appearance of metastasis while avoiding the adverse effects associated with conventional chemotherapy.

The CXCR4 receptor is overexpressed in at least 20 different cancer types, including prostate, breast, ovary and others not as common as the pancreas. This means that the nanoparticle can achieve targeted drug delivery in different tumor types, therefore, being a highly versatile vehicle that could transport different highly potent therapeutic molecules.

Currently, no drug in the market is capable of selectively eliminating metastatic stem cells. Therefore, this new discovery could have a high clinical impact, after carrying out the required regulatory studies, before their application in humans. The Hospital de la Santa Creu i Sant Pau in Barcelona would be the first Centre in the world to evaluate this drug in humans, prior to its possible introduction in clinical therapy.

Nanoligent, a new spin-off to finance the nanoparticle

In June 2017, researchers from the IIB-Sant Pau, the Institute of Biotechnology and Biomedicine at the UAB and the CIBER-BBN, who sign the article now published in EMBO Molecular Medicine, created a spin-off, Nanoligent, with the goal of developing the first drug designed to eliminate metastatic cells that could enter the market.

This company, which has more than 10 years of studies behind, is directed by Dr. Manuel Rodríguez Mariscal, a professional with a long experience in the field of investment and the creation of biotechnology companies and aims to obtain founding for the realization of the project.

Researchers from the Centro de Investigación Biomédica en Red de Enfermedades Cardiovascular (CIBERCV) of the Joan Cinca de San Pablo group have recently described a new technique to identify areas of scarring in patients with myocardial infarction by means of endocardium mapping of tissue electrical impedance.

In a preclinical study carried out in a porcine model of chronic myocardial infarction, it is evident that this procedure can allow recognition of the scar of the infarction and, theoretically, is not influenced by changes in the cardiac activation sequence. “Accurate identification of scar areas is essential for electrical ablation of arrhythmias in patients with myocardial infarction to provide optimal results,”says Dr. Cinca.

Currently, the identification of scar areas is based on a voltage mapping, i. e., analyzing the voltage of local electrocardiograms, so CIBERCV researchers have opened a new way, according to the head of the group. “Our study shows the mapping of the electrical impedance brought advantages over voltage mapping and, therefore, the simultaneous use of both procedures will allow a better detection of fibrosis zones and, in short, better results in patients undergoing ablation of ventricular arrhythmias,”Cinca says.

A pioneering study
This CIBERCV study is the first of its kind to analyze the ability to recognize areas of heart attack scar using a novel viewpoint based on the measurement of the electrical impedance catheter, a heart property that is influenced by the intrinsic structural characteristics of tissue. Previous investigations showed that this impedance is less in the scar of the infarction than in the normal myocardium, and this circumstance allows the recognition of the necrotic region.

Reference article:
Endocardial infarct scar recognition by myocardial electrical impedance is not influenced by changes in cardiac activation sequence. Amorós-Figueras G, Jorge E, Alonso-Martin C, Traver D, Ballesta M, Bragós R, Rosell-Ferrer J, Cinca J. Heart Rhythm. DOI: https://doi.org/10.1016/j.hrthm.2017.11.031

Researchers at the Hospital Santa Creu i Sant Pau in Barcelona and Sant Joan de Reus, led by Francisco Blanco-Vaca and Juan Carlos Escolà-Gil, of the IIB Sant Pau and the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) have identified the Mechanisms for which lipoproteins that transport good cholesterol (HDL) lose their cardioprotective capacity in patients with family hypercholesterolemia.

The work, in collaboration with Finnish researchers, has been published in the Journal of the American College of Cardiology and shows that patients with familial hypercholesterolemia exhibit alterations in the activities of the main enzymes involved in the maturation of HDLs, which causes alterations in its composition and a reduction in its main cardioprotective function, its ability to prevent the accumulation of cholesterol in the macrophages of the arterial wall.

Lídia Cedó, the first signatory of the work, indicates that these findings “also found teenagers with family hypercholesterolemia, a very common disorder that affects more than 100,000 people in Spain, which affects the need for an early diagnosis that allows starting treatments Early men who reduce the risk of myocardial infarction in the future. ”

Family hypercholesterolemia is a disorder inherited mainly by mutations in the gene of the low density lipoprotein receptor and characterized by high levels of low density lipoprotein, which are often associated with low levels of HDL.

In the study, researchers Núria Plana and Lluís Masana from the Sant Joan de Reus University Hospital, CIBERDEM, José Luis Sanchez-Quesada from IIB Sant Pau (CIBERDEM), Miriam Lee-Rueckert and Petri Kovan from the Wihuri Research Institute and Matti Jauhiainen del Minerva Foundation Institute for Medical Research, all of them in Helsinki.

Reference item:

Altered HDL Remodeling and Functionality in Familial Hypercholesterolemia. Cedó L, Plana N, Metso J, Lee-Rueckert M, Sanchez-Quesada JL, Kovanen PT, Jauhiainen M, Masana L, Escolà-Gil JC, Blanc-Vaca F. DOI: 10.1016 / j.jacc.2017.11.035

Researchers from the Lipids and Cardiovascular Pathology Group of the IIB Sant Pau, directed by Vicenta Llorente Cortés, have recently published an article in the journal Scientific Reports together with other researchers from the Endocrinology and Nutrition Service, from the Cardiac Imaging Unit at Hospital Sant Pau and from the Cardiovascular Biochemistry Group of the Institut de Recerca. The paper demonstrates the potential of the sLRP1 biomarker as a non-invasive indicator of epicardial fat in patients with type 1 diabetes.
The development of trials based on this protein could pave the way for new clinical tools for metabolic risk stratification in patients with type 1 diabetes.

“Soluble LRP1 is an independent biomarker of epicardial fat volumen in patients with type 1 diabetes mellitas”.

The Cardiac Imaging Unit of the Clinical and Translational Cardiology Research Group of the Institut de Recerca de l’ Hospital de la Santa Creu i Sant Pau has signed a collaboration agreement with the Department of Information and Communication Technologies of the UPF. The overall objective is to develop computational methods and tools for medical imaging analysis, specifically based on the radiological characteristics of cardiac magnetic resonance imaging.
Radiomics is a recent discipline in medical physics that focuses on the extraction of quantifiable characteristics from various types of medical images (computed tomography, magnetic resonance imaging, positron emission tomography). The use of numerical algorithms makes it possible to extract features that are not obvious to the naked eye, and that contribute to improve and complete the diagnosis of various pathologies.

Researchers from the Centre de Recerca en Xarxa de Malalties Cardiovasculars (CIBERCV) of José Martínez González’s group at the IIB Sant Pau have shown that CCL20 protein levels are increased in patients with abdominal aortic aneurysms compared to healthy controls and, more importantly, respect atherosclerotic patients who are not aneurysmal. The study, led by Mercedes Camacho, investigates the expression of CCL20 and assesses its possible role as a biomarker to aid in the prognosis of patients with abdominal aortic aneurysm.

In this way, it is demonstrated that CCL20 and its CCR6 receptor are increased in aneurysm and that their circulating levels are higher in patients with this aneurysm than in healthy individuals and patients with non-aneurysmal arteriosclerotic disease. “This is undoubtedly a unique feature that is not seen when other cytokines are analyzed that are also found to be increased in abdominal aortic aneurysm and, therefore, CCL20 is particularly relevant in these patients,”Mercedes Camacho says. In addition, plasma levels of CCL20 predict with high sensitivity the presence of aneurysm.

Autoimmunity is known to play a role, not fully clarified, in the pathology of abdominal aortic aneurysm. CCL20 chemokines are involved in the development of autoimmune diseases, although their potential contribution to the development and progression of abdominal aneurysm is unknown.

This work shows an association of the CCL20 and its possible role as a biomarker of the disease, which opens new avenues of research, as the author of the CIBERCV study acknowledges.

“It is essential to find new specific biomarkers for early detection of disease and stratification of risk. In addition, the identification of new biomarkers could help to discover new pathways involved in the pathophysiology of AAA and thus discover new therapeutic targets for pharmacological intervention of the disease,”says Dr. Camacho.

An asymptomatic pathology
Abdominal aortic aneurysm, prevalent in elderly people in industrialized countries, is a pathology that consists of a localized and permanent dilation of the aorta, usually in its infrarenal portion. It is a disease that is mostly asymptomatically, so the diagnosis occurs in many cases casually and currently there is no drug treatment capable of limiting the progression of the aneurysm or preventing its rupture.

Link to reference article
Circulating CCL20 as a New Biomarker of Abdominal AorticAneurysm.
B. Soto, T. Gallastegi-Mossos, C. Rodríguez, J. Martínez-González, J.-R. Escudero, L. Vila & M. Camacho.
SciRep. 2017 Dec 11;7(1):17331. doi: 10.1038/s41598-017-17594-6.

A study by researchers from the Institut d’Investigació Biomèdica de Sant Pau (IIB Sant Pau) and the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) demonstrates the key role of the liver lipase enzyme in the accumulation of liver lipids and the development of adiposity.

The work has been published in the prestigious scientific journal Plos One.

Researchers from the CIBER of Diabetes and associated Metabolic Diseases (CIBERDEM) and the Institut d’Investigació Biomèdica de Sant Pau (IIB Sant Pau), have identified the mechanisms by which the enzyme hepatic lipase, associated with the presence of metabolic alterations, obesity and the development of hepatic steatosis (fatty liver), causes accumulation of hepatic lipids and the development of adiposity.

The team of researchers, led by doctors Juan Carlos Escolà-Gil and Francisco Blanco-Vaca (IIB Sant Pau /CIBERDEM), used a transgenic mouse model that expressed human liver lipase in the liver. They demonstrated that enzyme expression promotes in vivo liver lipogenesis through the induction of a transcription factor (Srebf1) that controls the expression of major genes involved in fatty acid biosynthesis.

Lídia Cedó, researcher at CIBERDEM at the IIB Sant Pau and first signatory of the work, explains that “this study has been able to demonstrate the key role of liver lipase in the regulation of liver metabolism of lipids and fatty tissue accumulation “.

The researchers also found that the expression of this enzyme increased the ability of fat tissue cells to hydrolyze triglycerides by another enzyme (lipoprotein lipase) and the accumulation of fatty acids.

Vicenta Llorente-Cortes, researcher at the CIBERCV/CSIC-ICCC and Juan Carlos Laguna and Nuria Roglans from the Faculty of Pharmacy of the University of Barcelona, among others, have also participated in the study, published in Plos One.

Reference article:

Cedó L, Santos D, Roglans N, Julve J, Pallarès V, Rivas-Urbina A, et al. (2017) Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake. PLoS ONE 12(12):e0189834.

The Rolling Stone magazine has highlighted Jordi Riba, from the Human Neuropsychopharmacology research group of the Sant Pau Institute for Biomedical Research (IIB Sant Pau), as one of the 25 influential people in the world in the future of science.
You can read the Rolling Stone magazine article by clicking here.

Dr. José Julve, from the IIB Sant Pau and Dr. Francisco Blanco Vaca, director of the Biochemistry Service of Sant Pau and PI of the Grupo de Bases metabólicos del riesgo cardiovascular del IIB, is the main author of an article published in Translational Research, The Journal of Laboratory and Clinical Medicine.

The article demonstrates an important alteration in fecal cholesterol excretion in a model of rodents of the Muridae family of diabetes and extreme obesity, due to an alteration of signaling that regulates this excretion and is controlled by an adjustable transcriptional factor for binders called LXR alpha that controls the entero-hepatic cholesterol transporters ABCG5/G8.

Although this finding corresponds to a specific animal model, bariatric surgery of patients with morbid obesity improved the liver expression of alpha LXR and ABCG5/G8 suggesting that these alterations in cholesterol traffic, which are known to favor the development of cardiovascular diseases, are observed in patients with morbid obesity and diabetes.

You can view the article in pdf in the attached file.

On Sunday 19 November will take place in Les Franqueses del Vallès the 6th. edition of the race “Los 10 kilómetros de Les Franqueses” with the collaboration of the Town Hall of this locality and the endorsement of the Catalan Athletics Federation. The collection of all the editions of the career is destined to the Clinical Research Group in Oncology of the IIB, led by Dr. Agustín Barnadas, specifically in the field of kidney cancer research, for which Dr. Pablo Maroto is responsible.

Registration: www.xipgroc.cat
More information: www.els10delesfranqueses.cat

We encourage you to participate in this race of solidarity with Research.

The Board of Trustees of the La Marató de TV3 Foundation has granted 694,987.51 euros to Sant Pau. Three projects out of the five applied for have been chosen to receive one of the 37 grants awarded by La Marató 2016 in projects focused on finding tangible advances in the prevention, treatment and rehabilitation of motor, sensory and cognitive disabilities that cause stroke and traumatic injuries to the spine and brain.

The three Sant Pau projects that have been financed by La Marató 2016 are the following:

Dra. Raquel Delgado Mederos
Cerebrovascular Diseases Unit, Neurology Service of Sant Pau.
Coordinated project “Stroke, stroke unit, rehabilitation, optics, diffuse correlation spectroscopy, cerebral blood flow, brain self-regulation.“, 298.000,00 €.

Dra. Elena Jiménez Xarrié
Sant Pau Research Institute
“Lipoprotein biomarkers to determine the inflammation of carotid plaque in ischaemic stroke.“, 197.575,00 €.

Dr. Gerard Urrutia Cuchí
Epidemiology Service of Sant Pau
“Effectiveness of a core stability exercise program on dynamic balance in seating, trunk control and functional rehabilitation in patients with subacute stroke: randomized clinical trial.“, 199.412,51 €.

The funds raised in the 2016 edition of La Marató, which amount to 11.3 million euros, will boost awareness and research on stroke and traumatic spinal cord injuries. The 70 award-winning teams will work over the next three years to gain more and more quality of life for people who have had a stroke or traumatic injury to the spine or brain. Of the total number of works, 17 are unitary and 20 are coordinated between two or more research institutions.

With these new 37 projects, La Marató has already added 794 in its 25 years of history, which have brought important results in the health of citizens and notable advances in knowledge, prevention, prognosis and treatment of multiple diseases.

The Joint Service of Angiology, Vascular and Endovascular Surgery of Sant Pau – Dos de Maig has published an original article in the European Journal of Vascular and Endovascular Surgery describing the application of software originally developed in the fields of engineering and architecture for the calculation of strength of materials. This software is based on finite element analysis.
The application of this technology in patients with abdominal aortic aneurysms could help in assessing the risk of rupture and open a new avenue in deciding which patients and when they should have surgery.
This study is a joint work of the Joint Service of Angiology, Vascular and Endovascular Surgery of Sant Pau – Dos de Maig, IIB Sant Pau, UAB and CIBER of cardiovascular diseases.
More information (pdf artícle)

The Memory Unit of the Neurology Service of Sant Pau has recently published an article in the scientific journal Nature Genetics about a study on Alzheimer’s disease. The article “Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease”can be found in the attached document.

Dr. Jaume Kulisevsky, scientific director of the “Institut de Recerca de Sant Pau”; director of the Parkinson’s and Movement Disorders Unit, of the Neurology Service of Sant Pau and Adjunct Professor of Neurology and Speech Therapy in the Department of Medicine, is the new postgraduate vice-dean at the Faculty of Medicine, Autonomous University of Barcelona. Dr. Kulisevsky will also be co-ordinator of the Master’s Commission and a member of the Academic Council of the Graduate School on behalf of the Faculty of Medicine.

A team of scientific and clinical researchers from the Spanish Network of Research on Anemia of Fanconi, coordinated by the Division of Innovative Therapies of CIEMAT, demonstrates for the first time that gene therapy in stem cells of patients with Fanconi’s Anemia is feasible. Dr. Surrallés, director of the Genetics Service of Sant Pau, has participated in this finding, which has been published in the most prestigious journal of Hematology: BLOOD.

In their article, the researchers show that the gene correction procedure based on their own technology allows us to correct the pathology of the stem cells in these patients’ bone marrow.

The demonstration is based on a protocol for the genetic correction of hematopoietic stem cells in patients. After their mobilization in the patients’ blood, stem cells were corrected with clinically used viral vectors, and a very small part of them were transplanted to immunodeficient mice, in which human blood cells can be generated.

In this way, scientists have shown for the first time that through a gene therapy procedure, stem cells from patients with Fanconi’s anemia can generate disease-free human blood cells in transplanted mice.

These findings are a major boost that reinforces the researchers’ hypothesis that gene therapy will be a new way to effectively treat patients with Fanconi’s anemia. It is also of particular interest to the expectations of a clinical trial of gene therapy for these patients, which is currently underway in Spain and will soon be opened in other European countries.

This finding has been published in the most prestigious journal of Hematology: BLOOD

The news has also been highlighted by the weekly “Cell Therapy News”  on August 21 as Top Story by this newspaper.

Dr. Juan Cinca has been appointed member of the Advisory Council on Research and Innovation in Health (CAPRIS) of the Generalitat de Catalunya, a body created last December 2016.

Capri was conceived as the highest body advising the Ministry of Health in the development of policies in the areas of research and innovation.

Dr. Pablo Alonso Coello, researcher Miguel Servet of the Cochrane Center Iberoamericà / IIB-Sant Pau, is on the list of the most cited scientists in the world published by Clarivate Analytics, former branch of the Thomson Reuters agency dedicated to intellectual property and science.

The list includes the world’s top 3,000 researchers from 21 fields of science and social sciences, ranging from clinical medicine and neuroscience to agriculture, economics and the environment. Of these, 56 are researchers working in Spanish institutions, 7 of them linked to some CIBER, as is the case of Dr. Alonso who belongs to CIBERESP (CIBER of Epidemiology and Public Health).