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Posts on Jan 1970

Rare diseases Day February 29: combating Fabry Disease

29 of February is a ‘rare’ date and February, a month with a ‘rare’ number of days, has become a month to raise awareness about rare diseases and their impact on patients’ lives.  Since 2008 thousands of events happen every year all around the world and around the last day of February.

NanoMed Spain Platform and the Hospital of Sant Joan de Déu have organized the NanoRareDiseaseDay to present the latest innovations in the field of Nanomedicine for the treatment and diagnosis of rare diseases (diseases affecting less than 5 people per 10,000 inhabitants). Nora Ventosa, Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit  (CIBER-BBN / ICMAB-CSIC) presented Smart4Fabry a European project with the aim of reducing the Fabry disease treatment cost and improve the life-quality of Fabry disease patients

Fabry disease is one of the rare diseases that currently lack a definitive cure. It is cause by lysosomal storage disorders (LSDs):  the deficiency of α-Galactosidase A (GLA) enzyme activity result in the cellular accumulation of neutral glycosphingolipids, leading to widespread vasculopathy with particular detriment to the kidneys, heart and central nervous system.

Smart-4-Fabry has been conceived to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration compared to the actual treatment with non-formulated GLA. Four units of NANBIOSIS participate in the project:

U1 Protein Production Platform (PPP) led by Neus Ferrer and Antony Villaverde at IBB-UAB accomplish the production and purification in different expression systems for R&D purposes.

U3 Synthesis of Peptides Unit led by Miriam Royo at IQAC-CSIC performs all the chemical process of the Smart-4-Fabry  project, i.e. design and synthesis of peptides used as targeting ligands in the nanoliposome formulation

U6 Biomaterial Processing and Nanostructuring Unit led by Nora Ventosa and Jaume Veciana at ICMAB-CSIC undertakes tasks related to the manufacture of the nanoliposome formulation of GLA enzyme and the physico-chemical characterization (this unit counts with plants at different scales, from mL to L, which allow process development by QbD and process scale-up, as well as instrumental techniques for assessment of particle size distribution, particle concentration, particle morphology and stability, and Z-potential)

U20 In Vivo Experimental Platform led by Simó Schwartz and Ibane Abásolo at VHIR to carry out the non-GLP preclinical assays of the project (in vivo efficacy, biodistribution and tolerance/toxicity assays).

For further information about Fabry disease and the Smart4Fabry project: here

Nora Ventosa explaining the progress of the smart4fabry
project on nanoliposomes development for the treatment of Fabry disease
(Pictures by Nanomed Spain)
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Fabry disease & Smart4Fabry project

The Fabry disease (FD) is a lysosomal storage disorder (LSD) that currently lacks an effective treatment. Lysosomes are spherical vesicles, which contain hydrolytic enzymes found in nearly all animal cells. LSDs are caused by lysosomal dysfunctions, usually because of the deficiency of a single enzyme required for the metabolism of macromolecules such as lipids, glycoproteins and mucopolysaccharides. Fabry disease is a progressive, X-linked inherited disorder caused by deficiency or absence of the α-galactosidase A (GLA) activity, an enzyme involved in the glycosphingolipid metabolism. The substrates of GLA are glycosphingolipids, being the primary substrate the globotriaosylceramide (Gb3). Therefore, the failure of GLA activity leads to progressive intracellular accumulation of Gb3, in many cells, particularly in renal epithelial cells, endothelial cells, pericytes, vascular smooth muscle cells, cardiomyocytes, and neurons of the autonomic nervous system, leading to multisystemic clinical symptoms. First clinical signs of FD occur during childhood and, over time, microvascular lesions of the affected organs progress leading to early death. It affects mostly men but serious cases have also been reported in women.

There are currently three products authorized in the EU for the treatment of FD. Two products available in EU since 2001 for Enzymatic Replacement Therapy (ERT), Replagal (Shire Human Genetic Therapies AB) and Fabrazyme (Genzyme Europe B.V.), which have to be i.v. administered every other week. The ERT strategy is based on supplying recombinant GLA to cells, reversing several of the metabolic and pathologic abnormalities. There is a third product in the EU market since 2016, which is based on the chaperone migalastat hydrochloride (Galafold Amicus Therapeutics UK Ltd), designed to selectively and reversibly bind with high affinity to the active sites of certain mutant forms of GLA, facilitating proper protein folding and allowing for correct trafficking of the mutant enzyme. However, it is a genotype-specific treatment (only one-third to one-half of mutations may be amenable).

To date, no direct comparisons exist between Fabrazyme and Replagal but significant clinical benefits compared with placebo, however, have been demonstrated with ERT, with positive effects on the heart, kidneys, nervous system and quality of life. Of note, a stabilization of renal function was only observed at an early phase of FD.

ERT success with free GLA is limited mainly due to the instability and low efficacy of the exogenously administered therapeutic enzyme. Furthermore, some patients can develop immune responses after receiving the infused recombinant enzyme. Clinical data has confirmed that the immunological consequences of ERT may impair efficacy in some patients. Furthermore, the short elimination t1/2 of the enzyme and the need for repeated administration of large amounts of enzyme are other limitations of current ERT. In addition, GLA does not cross of the Blood Brain Barrier (BBB), which prevents the product for reducing the Gb3 deposits in the central nervous system (CNS). Moreover, it is a lifelong treatment which becomes a burden for the health system due to its extremely high cost.

Therefore, there is a need for other therapeutic strategies, which can either serve as primary or supplemental treatments. Gene and substrate reduction therapies constitute alternative therapies which are at present under investigation.

The European “Smart-4-Fabry” project aims to develop a new nanoformulation based on the encapsulation of the GLA enzyme in nanoliposomes, to improve the current ERT of FD. A Consortium formed by ten partners, including private companies and public institutions in Europe and Israel, has been granted (July 2017) with a Horizon2020 financial programme by the European Commission (H2020-NMBP-2016-2017; call for nanotechnologies, advanced materials, biotechnology and production; Proposal number: 720942-2).

The project is expecting to last for 48 months and contemplates the necessary activities to advance a nanoliposome formulation of GLA enzyme, i.e., nano-GLA, from an experimental proof of concept up to an advanced nonclinical stage of development. The S4F should complete an advanced regulatory safety and toxicology package supporting future nano-GLA clinical development in patients with FD.

To the best of S4F knowledge, there is no previous experience on the encapsulation of a GLA for treating FD patients following an ERT approach.

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Course on Coloretal Endoscopy for Surgeons

JUMISC and the Spanish Association of Coloproctocology has organised the ICourse on Coloretal Endoscopy for Surgeons which wil take place at JUMISC on March, 9 -10, co-Directed by  Fernando de la Portilla de Juan (President of Spanish Association of Coloproctology) and Francisco M. Sanchez Margallo (Deputy Scientific Director of NANBIOSIS)  

The course includes colonoscopy practices in pig and canine models.

For further information and inscriptions: here

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#RareDiseaseDay: Fabry lysosomal disease

Rare Disease Day is annually held on the last day of February in more than 100 countries with the main objective of raising awareness about rare diseases and their impact on the life of patients to the general public and in particular to policy makers, public authorities, industry representatives, researchers and professionals. Rare diseases are those that affect less than 1 in 2000 people. There are more than 300 million people living with one or more than more than 6000 rare diseases worldwide identified.

Among the events organized we wont to mention the Nano Rare Diseases Day held in Barcelona on February 27, organized by the Hospital de Sant Joan de Déu and the NanoMed Spain Platform, where the latest innovations in the field of Nanomedicine for the treatment and diagnosis of these diseases will be announced, with themes ranging from early diagnosis, controlled release of drugs or the development of new therapies. During this day, experts in Nanomedicine from different fields – research, business, clinical practice, health authorities, patients, etc. – will present the latest advances and give us the opportunity to discover the progress generator that Nanomedicine means for health as creator of new opportunities in the diagnosis and treatment of minority diseases.

Nora Ventosa, Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit (CIBERBBN-ICMAB_CSIC) will explain the European Smart-4-Fabry Project: use of nanotechnology for the development of a new drug for the treatment of Fabry lysosomal disease  where four units of NANBIOSIS colaborate.


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Preliminary Market Consultation (CPM): technology development in the field of organ preservation.

The Center for Industrial Technological Development (CDTI) has selected the proposal presented by JUMISC, partner of NANBIOSIS, on the technological challenge of an alternative cold preservation system in a preliminary market consultation.
On February 4, the Technical Conference of the Preliminary Market Consultation of the Organ Preservation Challenge was held.
The objective of the Preliminary Market Consultation was to obtain information from the market operators in the Organ Preservation technologies in order to adequately define the future potential for pre-commercial Public procurement and adequately inform the economic operators of the requirements that will be required in the Potential future tender for pre-commercial public purchase.
The Conference was directed by Ms. Ana Isabel Rodríguez Belda, Innovative Public Procurement Technician of the CDTI and Mr. Franciso M Sánchez Margallo, Scientific Director of JUMISC and Deputy Director of NANBIOSIS who, after reviewing the background and problems related to the preservation of organs for transplantation, he presented the technological challenge presented by JUMISC and selected by the CDTI and how its preclinical animal validation in JUMISC can be of great help in human ogan transplants
The conference included a visit to the facilities of CCMIJU, partner of NANBIOSIS ICTS

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Organ-on-chip monitoring. Breakthrough technological approximations

Organ-on-chip (OOC) is the term used to define a microfluidic 3D culture model that contains continuously perfused chambers inhabited by living cells. OOC are considered as very promising tools for investigating many aspects of human physiology and pathophysiology as well as drug testing platforms with future progressions to be used for precision medicine.

As the complexity of OOC systems increases, the necessity to integrate relevant assessment methods to provide information about cell physiology, secreted metabolites as well as pharmacodynamics drug responses also increases. Dr. Rosa Villa, who leads NANBIOSIS U8 Nano Technology Unit and the Biomedical Applications Group of the Institute of Microelectronics of Barcelona and CIBER in Bioengineering, Biomaterials and Nanomedicine, works on different engineering approaches to develop physical and chemical sensors that can be integrated into the OOC devices. The group considers that sensors integration is a requirement that must be taken into consideration in an OOC platform giving the necessary assessment of the OOC platforms in a continuous and real-time

An overview of the most relevant works of the Biomonitoring Group and NANBIOSIS Unit 8 have been presented by Mar Alvarez and Gemma Gabriel, researchers of
NANBIOSIS U8 Nano Technology in the conference on Engineering Multicellular Systems organized by EMBL – IBEC that took place in La Pedrera Auditorium, in Barcelona, from 10-12th February 2020.

It has been presented a device fabricated for that mimics Retina. In this novel microfluidic device cells are arranged in parallel compartments and are highly interconnected through a grid of microgrooves, which facilitates paracrine signaling and heterotypic cell–cell contact between multiple tissues. In the field of Brain, TEER barrier monitoring is mandatory. An interdigitated electrodes (IDE) configuration where the entire cell culture area contributes equally to the measurement, has been integrated in a custom-made bioreactor. This configuration, besides being more accurate for measuring the TEER, also allows the minimal electrode coverage, so that the optical visualization of the cell culture is maximized. The control and monitoring of dissolved oxygen (DO) is key for most of the OOC. The integration of oxygen sensors in an Liver-On-a-Chip system to achieve in-situ and real-time monitoring of oxygen zonation along the cell culture microfluidic chamber. A miniaturized sensing device compatible with microfluidic technology to measure simultaneously dissolved oxygen, pH, Na+ and K+, able to be connected in the input or output of a cell culture system has been developed for Kidney monitoring.


[1]   Yeste J, García-Ramírez M, Illa X, Guimerà A, Hernández C, Simó R, Villa R, “A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood–retinal barrier” Lab on a Chip 18 (2018) 95-105

[2] Yeste J, Martínez-Gimeno L, Illa X, Laborda P, Guimerà A, Sánchez-Marín JP, Villa R, Giménez I “A perfusion chamber for monitoring transepithelial NaCl transport in an in vitro model of the renal tubule “, Biotechnology and Bioengineering 115 (2018) 1604-1613

[3] Moya A, Ortega-Ribera M, Guimerà X, Sowade E, Zea M, Illa X, Ramon E, Villa R, Gracia-Sancho J, Gabriel G., “Online oxygen monitoring using integrated inkjet-printed sensors in a Liver-On-a-Chip system” Lab on a Chip (2018),18, 2023-2035

[4]Moya A, Illa X, Gimenez I, Lazo-Fernandez Y, Villa R, Errachid A, Gabriel G. “Miniaturized multiparametric flexible platform for the simultaneous monitoring of ionic compounds: Application in real urine” Sensors and Actuators B: Chemical 255 (2018) 2861-2870

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Challenges in precision medicine

Transfiere, the European Forum for Science, Technology and Innovation,  the bigest professional and multisectoral forum for the transfer of knowledge and technology held in Spain, took place last February 12 and 13 in Malaga in its 9th edition.

Among the events held at Transfiere, there has been a round table organized by all health-related platforms under the title: Challenges in precision medicine on the 12th at 6pm.

Maria Luisa García Martín, Scientific Director of NANBIOSIS U28 of Nanoimaging Unit and head of Nano-Imagen  facilities at BIONAND, was invited by the Nanomedicine platform, NanomedSpain as a speaker at the aforementioned round table to discuss metabolomics and cancer. The rest of the participants were:

• Amelia Martín Uranga. Responsible for the Innovative Medicines Platform (Pharmaindustry) – Data protection in precision medicine.

• Beatriz Palomo. Coordinator of Biotechnology Markets Platform Responsible for projects and the ASEBIO Health Area

• Patricia Fernández. Coordinator of the Vet + i-Spanish Technology Platform for Animal Health Foundation

• Antonio Riobás. Medical Director and Health Advisor at Biocrew – Aspects of meso and micro-management in relation to the incorporation of Precision Medicine. Spain and its challenges.

Among subjects discussed, ethical aspects, data protection, limitations and challenges to overcome, the role of patients and clinicians, as well as the role of new technologies, such as metabolomics, in precision medicine, Maria Luisa García shared her experience about  the role of magnetic resonance metabolomics in the precision medicine of the futue, focused on tumor diagnosis.

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Mechanism and Consequences of the Impaired Hif-1α Response to Hypoxia in Human Proximal Tubular HK-2 Cells Exposed to High Glucose

NANBIOSIS has been informed about a recent publication in the pretigious scientific magzine SCIENTIFIC REPORTS (Q1) of Nature Research group, mentioning NANBIOSIS Unit 17 in the Methods section:

Immunofluorescence analysis: Detection was performed by using a Leica SP5 confocal microscope (Leica Microsystems, Wetzlar, Germany), through the Confocal Microscopy Service of the ICTS ‘NANBIOSIS’ Unit 17 of the Biomedical Research Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the University of Alcalá, Madrid, Spain. HIF-1α-dependent immunofluorescence intensity was quantified after digital capture using image-J software.

The Leica TCS-SP5 confocal microscope with especial features allows studying interactions between cells/tissues and materials. Indeed, the experience of the research group in charge of this service makes it a unique service for the study of cells and tissues and the interactions between various materials and cell components as well as between implants/scaffolds and tissues of the recipient organism

Article of reference:

Mechanism and Consequences of the Impaired Hif-1α Response to Hypoxia in Human Proximal Tubular HK-2 Cells Exposed to High Glucose. Coral García-Pastor, Selma Benito-Martínez, Victoria Moreno-Manzano, Ana B. Fernández-Martínez, Francisco Javier Lucio-Cazaña. SCIENTIFIC REPORTS, (2019) 9:15868 | https://doi.org/10.1038/s41598-019-52310-6

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VII Course of Microscopic and Piezoelectric Techniques in Dentistry: Endodontics, Implantology and Prosthetics

CCMIJU has organised the VII Course of Microscopic and Piezoelectric Techniques in Dentistry: Endodontics, Implantology and Prosthetics, which wil take place at JUMISC from March 3 till June 27 2020 under the Direction of Alberto Anta Escudero. (Profesor of the UPV-EHU), Gorka Santamaría Arrieta (Professor of the UPV-EHU), Jon Eskurza Pérez (Endodontics Specialist. Private Clinic) and Francisco Miguel Sánchez Margallo (Deputy Scientific Director of NANBIOSIS)

The general objective of the course is the knowledge of the enodontology magnification, necessary materials and instruments and related ergonomic aspects. Training in magnification in dentistry

Frurther information: Programm and inscriptions

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In order to achieve full and equitable access and participation in science for women and girls, and also to achieve gender equality and the empowerment of women and girls, the United Nations General Assembly decided to proclaim in 2016 (resolution A / RES / 70/212) February 11 as the International Day of Women and Girls in Science.

We want to take this day to congratulate all the women who lead research and innovation and contribute to the breakdown of the barriers that still exist, especially to the scientists from NANBIOSIS ICTS.

Happy International Day of Women and Girls in Science!

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