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News U20

News U20

Collaboration of two NANBIOSIS units in the Valorisation Project “ADVERT”

The Project ADVERT (Advanced Extracellular Vesicles for Enzyme Replacement Therapy) is a research valorisation project recently granted by CIBER.

The project pursues to advance the development of extracellular vesicles as treatments for lysosomal diseases, specially to bring new therapies to treat FABRY disease.

The ADVERT Project will count on the active particpation of two NANBIOSIS units of CIBER-BBN:

The project will be financed with € 20,000.

The CIBER-BBN transfer program

The CIBER-BBN transfer program through its call for transfer and valorization projects has been designed to promote the transfer to the industrial sector of scientific or technological results derived from the research carried out by the CIBER-BBN groups. These transfer projects will make it possible to support the commercialization of said results, since there is a company that has shown interest in them and that provides at least, the same financing than CIBER-BBN for their achievement.

The call for valorisation projects is in its fourth edition, having already financed a total of fourteen projects.

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Extracellular vesicles as vehicles for therapeutic enzymes in lysosomal deposition diseases

Researchers of two CIBER-BBN units of the ICTS (Singular Scientific and Technical Infrastructures) NANBIOSIS, led by Ibane Abasolo the U20 located in the VHIR and the U6 in ICMAB-CSIC have participated in a study to improve the treatment of lysosomal disorders.

In recent years, enzyme replacement therapies (ERTs) based on the systemic administration of a functional version of the defective enzyme have gained clinical relevance as a treatment for lysosomal storage disorders (LSD). However, the systemic administration of these recombinant enzymes has negative aspects, such as their low stability and inadequate distribution to the affected organs that result in a limited efficacy of ERT. In this context, the Vall d’Hebron Research Institute (VHIR) has led a study that has analysed the use of extracellular vesicles as vehicles for therapeutic enzymes in this type of lysosomal storage disorders. This work, in which the CIBBIM-Nanomedicine, Drug Delivery and Targeting, led by Dr. Ibane Abasolo and investigator Guillem Pintos, and Neurovascular Diseases, led by Dr. Anna Rosell, of the VHIR have participated, has been published in the Journal of Extracellular Vesicles.

Lysosomal storage disorders are rare congenital diseases caused by the lack or malfunction of proteins involved in lysosomal biogenesis and activity. In the absence of activity of these proteins, lysosomes accumulate waste molecules inside. Although there are more than seventy types of LSD – among which are the Gaucher, Fabry, Pompe and Sanfilippo syndromes – all of them share the abnormal accumulation of molecules such as glycoproteins, glycosaminoglycans and sphingolipids, something that in the majority of the cases generates serious clinical manifestations.

The symptoms that the patient may experience depend on the specific disorder they develop, but in general LSDs results in a systemic disease that can affect multiple organs, including the central nervous system, liver, kidneys, heart and musculoskeletal system”, says Dr. Ibane Abasolo, principal investigator of the research group in CIBBIM-Nanomedicine, Drug Delivery and Targeting of the VHIR and author of the study. All LSDs are rare diseases and their low incidence makes it difficult to develop new therapies and evaluate them in clinical trials. For all these reasons, the VHIR has wanted to participate in this work, which has analysed and tested the viability of a new therapy for this type of lysosomal storage disorders. Specifically, for Fabry and Sanfilippo A diseases, two of the LSDs with the highest prevalence.

The study has obtained extracellular vesicles loaded with therapeutic enzymes directly from cells that are used for the production of recombinant protein. Extracellular vesicles have been shown to function as highly efficient protein delivery platforms, also in the brain, an organ that is not naturally accessed by systematically administered proteins. Dr. Abasolo considers that “the results obtained in this work will lay the foundations for the implementation of replacement therapy driven by extracellular vesicles in different LSDs, and will open the way for a possible treatment strategy in disorders with central nervous system involvement”.

The following centres have also participated in this work: Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (IBB-UAB), Centre for Biomedical Research in Network of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Bioengineering of Catalonia (IBEC), Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), and Centre for Biomedical Research in Network on Liver and Digestive Diseases (CIBEREHD).

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Simo Schwartz: new General Director of the Bank of Blood and Tissues of Catalonia.

Simó Schwartz Jr., Scientific Director of NANBIOSIS Unit 20 In Vivo Experimental Platform has been appointed as the new general director of the Bank of Blood and Tissues of Catalonia, replacing Enric Argelagués, who is leaving his post after 17 years as director. Argelagués was the promoter of the unification of blood banks that began in the eighties and culminated in the current Bank of Blood and Tissues of Catalonia.

Simó Schwartz now assumes the executive management of the organization, which currently has more than 800 workers and its mission is to ensure that all people in Catalonia have the blood and tissues necessary for their treatment at their disposal, promoting proper use. It is a reference center in diagnostic immunology and in the development of advanced therapies, it is present in the main hospitals in Catalonia and is part of the national and international organizations related to donation, transfusion and treatments with biological components.

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A more effective nanomedicine has been developed for the treatment of Fabry rare disease.

28 February: International Rare Disease Day

  • This is one of the major achievements of the European Smart4Fabry project, which is now coming to an end after four years of work.
  • The results have been made possible by nanotechnology and the approach developed could be applied to other drugs in the future.
  • The new drug improves on current treatments and helps reduce costs and improve patients’ quality of life.

Barcelona, 26 February 2021.- The advance of nanomedicine opens up new possibilities in the development of drugs, such as the one recently developed for the rare disease Fabry, with improved efficacy compared to existing authorised treatments.

Thus, the European Smart4Fabry project has come to an end with one of the best results possible: the designation of a new orphan drug by the European Commission and the possibility of making progress in the treatment of Fabry, a rare disease that is estimated to affect approximately 2.6 out of every 10,000 people in the EU.

It is a chronic debilitating disease due to recurrent episodes of severe pain that is difficult to control with conventional analgesics, and it is life-threatening due to renal failure and associated cardiovascular and cerebrovascular complications.

With this designation we have made a major achievement, not only for Fabry patients, but also for other pathologies that can benefit from this same approach, made possible by nanotechnology,” explained Nora Ventosa, Scientific Director of NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring Unit of CIBER-BBN and ICMAB-CSIC who coordinated the project.

Need for new treatments for the disease

This disease, also known as Anderson-Fabry disease, represents the most common lysosomal storage disorder. It is caused by an absence or deficiency of the enzyme α-galactosidase A (GLA), which results in the lysosomal accumulation of globotriaosylceramide (Gb3) and its derivatives in the lysosomes of a wide variety of tissues, responsible for the clinical manifestations. Current treatments consist of intravenous administration of the GLA enzyme, but have limited efficacy and poor biodistribution.

The drug that has been developed is a new nanoformulation of GLA (nanoGLA) that improves efficacy compared to the reference treatment with non-nanoformulated GLA. “The third-generation liposomal product we have developed in the project has demonstrated, at preclinical level, improved efficacy, compared to authorised enzyme replacement treatments, demonstrating that the strategy of supplying the affected cells with the GLA enzyme via the smart nanoliposome is highly successful”, explained Ibane Abasolo, Scientific Coordinator of NANBIOSIS U20 of CIBER-BBN and VHIR, who is responsible for the efficacy studies in the project.

The nanoGLA product was obtained using DELOSTM formulation technology, an innovative platform for the robust production of nanomedicines in an efficient and sustainable manner.

The Committee for Orphan Medicinal Products, the European Medicines Agency’s (EMA) committee responsible for recommending orphan designation of medicines for rare diseases, has considered these results to have a clinically relevant advantage over current enzyme replacement therapies.

The designation of orphan drug, in addition to recognising the significant benefit of the new nanomedicine over products already licensed for Fabry disease, has important implications for the translation of the new therapeutic product from bench to bedside.

Those responsible for these results, including several CIBER-BBN groups, highlight that the new formulation helps to improve treatments, reduce costs, and improve the quality of life of Fabry patients.

Interdisciplinarity and public-private collaboration

The Smart4Fabry project has been running since 2017 thanks to European funding of €5.8 million, from the Horizon 2020 programme. This was possible thanks to the collaboration of several CIBER-BBN groups and NANBIOSIS Units at the Institute of Materials Science of Barcelona (ICMAB-CSIC) with the abouve mentioned NANBIOSIS Unit 6, the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) with NANBIOSIS Unit 3 of
Synthesis of Peptides Unit
, led by Miriam Royo, the Vall d’Hebron Research Institute (VHIR) with NANBIOSIS Unit 20 and the Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (IBB-UAB) with NANBIOSIS Unit 1 Protein Production Platform (PPP), whose work in this project was led by José Luis Corchero. It has also been necessary to contribute knowledge from different academic and business disciplines.

The project consortium also includes public institutions such as the University of Aarhus (Denmark), Technion Israel Institute of Technology (Israel) and Joanneum Research (Austria); and the companies Biokeralty (Spain); Nanomol Technologies SL (Spain); BioNanoNet (Austria), Drug Development and Regulation SL (Spain), the Covance Laboratories LTD group (UK) and Leanbio SL (Spain), which have provided the necessary expertise in nanotechnology and biotechnology, physicochemical characterisation, in vitro and in vivo biological evaluation, formulation and grading of nanomedicines, and pharmaceutical development and production under the guidelines of regulatory agencies.

CIBER and CSIC, promoters of orphan drugs

Orphan Drug Designations (ODDs) seeks to facilitate the arrival of treatments for rare diseases on the market. Several incentives are associated with ODDs, such as market exclusivity, fee reductions and specific scientific advice.

To date, CIBER has promoted eleven orphan drugs designated by the EMA, mainly from the thematic area of Rare Diseases (CIBERER), this being the first from CIBER-BBN.

On the other hand, this is the fourth ODD that the CSIC has obtained, and the first time it refers to a nanoformulated drug.

Orphan drug designation by the European Medicines Agency has several advantages, such as receiving a commercialisation authorisation for 10 years during which similar products cannot be commercialised, the availability of free or low-cost scientific advice and support protocols, and exemption from designation fees. In addition, entities developing orphan drugs have access to specific grants from the European Union and member states’ programmes.

More information

Scientific Culture Unit UCC+i CIBER cultura.cientifica@ciberisciii.es

Other related news

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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in NANBIOSIS, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer and Mercedes Márquez in the Scientific Direction and Coordination of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín and Margarita Hierro in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Isolda Casanova in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 
Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS, Anna Aviñó in the Scientific Coordination of U29 Oligonucleotide Synthesis Platform (OSP) – and

Nerea Argarate in the coordination of NANBIOSIS

Thanks to all of you and your teams!

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Nanoparticles to eradicate Cancer Stem Cells

Colorectal cancer (CRC) has a high prevalence worldwide and resistance to conventional chemotherapies and tumor relapse are usually related with a population of cells with malignant properties – Cancer Stem Cells (CSC).

Scientists of CIBER-BBN and VHIR have led a research with the goal not only to treat the primary CRC, but also eradicate CSC. For both purposes, the use of nanoparticles (NP) is a useful strategy. These “bullets” carrying a drug in its core, are able to reach tumor tissue due to its small size. Cancer cells, and in particular CSC, present at their surface receptors that could be specifically recognized by molecules used to decorate NP, driven the drug of interest to these cells. In this work we developed a type of NP decorated with an antibody fragment that specifically recognize the receptor CD44v6, which is overexpressed in CSC and was previously demonstrated to be present in patients with metastasis and poor-prognosis. Moreover, researchers have encapsulated Niclosamide (NCS), a drug that demonstrated efficacy against breast CSC, inside their NP.  NP increased the efficacy of NCS and​ accumulated in the tumors reducing its systemic exposure and increasing safety. Most importantly, the developed system significantly reduce circulating tumor cells, precursors of metastasis, reducing CSC malignancy.

This system has the potential to create a new therapeutic approach that could bring a new hope for CRC treatment and prevention of cancer relapse.​

The work has been developed at the group of CIBBIM-Nanomedine_Drug Deliver & Targeting of Vall d’Hebron Institute of Research (VHIR) and CIBER-BBN, in collaboration with Bruno Sarmento (University of Porto, Portugal) and Marika Nestor (Uppsala University, Sweden) that helped to developed the NP and the targeting antibody, respectively. In vivo assays on the safety and efficacy of the NPs were conducted thanks to the contribution of the FVPR/U20 of ICTS-Nanbiosis. ​

Article of reference

Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernández, Sara Montero, Francesc Martínez-Trucharte, Joaquin Seras-Franzoso, Zamira V.Díaz-Riascos, Ana Boullosa, Natalia García-Aranda, Patricia Cámara-Sánchez, Diego Arango, Marika Nestor, bane Abasolo, Bruno Sarmento, Simó SchwartzPolymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo Journal of Controlled Release Volume 331, 10 March 2021, Pages 198-212 https://doi.org/10.1016/j.jconrel.2021.01.022

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New spin off of VHIR “BSURE Medical” led by Simó Schwartz (NANBIOSIS U20)

Dr. Simó Schwartz, Scientific Director of NANBIOSIS U20 and head of the “Drug Delivery and Targeting group” of CIBER-BBN and VHIR, toghether with Dr. Jaume Alijotas (VHIR), have promoted the creation of the Spin-off ·BSURE Medical· for the devlopment of products and services for the diagnosis, prevention and consultation of aspects related to treatments with all types of bioimplants.

One of the objectives of the Drug Delivery and Targeting group is to carry out preclinical studies to determine the effects and toxicities of drug delivery systems, cell therapies and biomaterials. Studies chace been carried out through the Nanbiosis unit U20, of which the CIBBIM-Nanomedicine platform for functional validation and preclinical studies (FVPR) is a part. The group’s interest in studying the immune-related adverse effects caused by different biomaterials, allowed the identification and validation in two clinical studies of the predictive use of specific genetic biomarkers associated with severe late responses caused by injectable biomaterials, the basis of the new company BSure Medical.

Dr. Jaume Alijotas and Simó Shwartz have led the development of a procedure that makes it possible to determine, reliably and easily the risk of suffering serious late-onset immune, local, regional or systemic adverse effects (edema, angioedema, induration of skin, multiple inflammatory nodules, panniculitis, even granulomatous or autoimmune diseases…) after implantation of an injectable biomaterial, such as dermal or subcutaneous fillers. This risk is strongly associated with the presence of certain antigen profiles in a biological sample of the individual, which allows them to be easily identified from the analysis of blood or saliva samples.

The technology is patented and has been validated in two independent clinical trials coordinated by the Systemic Autoimmune Diseases Unit of the Vall d’Hebron University Hospital in Barcelona and by the Dermatology Department of the Erasmus Medical Center, Rotterdam and the Department of Plastic Surgery, VU University Medical Center, Amsterdam. The VHIR has granted BSURE a license to use and exploit it exclusively and worldwide. The patent has already been granted in Europe, Brazil and Japan

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Smart-4-Fabry final workshop

Next Wedneday, February 3, 2021 will take place the on-line event Smart-4-Fabry Final Workshop.  

Smart-4-Fabry is a european project, coordinated by CIBER-BBN wich has been developed during four years. This project is a sign of cooperation at European level to boost nanomedicine development and translation to clinical stages.

This project is also a clear example of the relevance of access to advanced research infrastructures as NANBIOSIS -ICTS. Four NANBIOSIS units have collaborated and contributed to Smart-4-Fabry development:

“The Fabry disease (FD) is a lysosomal storage disorder (LSD) that currently lacks an effective treatment” as Prof. Nora Ventosa, IP of the project, explained for NANBIOSIS blog – The aim of Smart-4-Fabry is to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration compared to the actual treatment with non-formulated GLA.

In the final workshop experts will talk about how, why and for what the solution proposed by Smart4Fabry was conceived.

Registrations and program at https://smart4fabry.cientifis.com/

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New patented peptide to allows the faster internalization of drugs within cells and the design of more effective therapeutic nanoconjugates

Researchers of NANBIOSIS Unit 20 In vivo Experimental Platform of CIBER-BBN and Vall d’Hebron Research Institute (VHIR) have patented a peptide that, in comparison to the current standard treatment, is much faster, internalizes much more, and does not cause any toxicity.

The membrane of a cell is an effective barrier that hinders the targeted delivery of molecules, such as therapeutic compounds. During the last years, several strategies have been developed to get the molecules into the cell interior but, in general, the methods developed still show a low efficacy and / or toxicity. “The use of therapeutic nanoconjugates such as nanomedicines facilitates the transport and delivery of drugs in target cells, but often with less efficiency than we would like,” says Dr Simó Schwart Jr, head of the Scientific Director of NANBIOSIS Unit 20 and the CIBBIM-Nanomedicine group: Direction i Alliberament Farmacològic del Vall d’Hebron Research Institute (VHIR)/CIBER-BBN.

Given the need to get more drugs or proteins into cells, one of the alternatives to be able to increase the amount that enters their interior more quickly is what is known as Cell penetrating peptides or cellular internalizing peptides, small sequences of amino acids that have the ability to interact with the plasma membranes of cells and, as a result of this interaction, make it easier to internalize the cargo they carry. An example of application would be when an internalizing peptide binds to a therapeutic nanoconjugate, achieving a greater capacity for the nanoconjugate to enter the cell interior and, therefore, to release the drugs it carries into the cells.

Until now, one of the most important internalizing peptides used has been known as TAT. Now, a team of researchers led by Dr. Schwartz Jr, has discovered a sequence common to a family of peptides that significantly outperforms the TAT results and facilitates the cellular internalization of nanoconjugates in a very significant way. These peptides are derived from a membrane protein called CD300 which has a very high capacity to interact with sphingomyelin, a lipid found in all plasma membranes and also in intracellular organelles. “The peptides in our patent”, explains Dr. Simó Schwartz Jr, “are derived from an extracellular part of CD300, which has a high capacity to bind sphingomyelin. Compared to the current standard treatment, TAT, CD300f7 is much faster, internalizes much more, and does not cause any toxicity. The use of these peptides in nanomedicine therefore facilitates and increases the internalization process of all the cargo they carry. This means that we are able to introduce drugs into cells in less time and in greater quantities ”. The results of this discovery not only allow for faster internalization within the cell, but also open the door to designing much more effective therapeutic nanoconjugates.

Souce of information: VHIR news

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CLINAM 2020: Clinical Nanomedicine and the Impact of Digitalization and Artificial Intelligence for Precision Medicine

CLINAM, the European Foundation for Clinical Nanomedicine will celebrate on October 26 – 28, 2020 the 12th European and Global Summit for Nanomedicine with the subject Clinical Nanomedicine and the Impact of Digitalization and Artificial Intelligence for Precision Medicine. The Technologies for Diagnosis & Therapy in Patient-Centric Medicine The Conference will take place in Live Stream, due to the COVID-19 pandemic.

NANBIOSIS will participate in the Virtual Enhibition and in the poster session with a poster “Cutting Edge Biomedical Solutions in Health for Translation into Clinics”. Also Prof. Simó Schwartz, Scientific Director of NANBIOSIS U20 In vivo Experimental Platform, will give a talk about “Delivery of AntiCancer stem cell drugs in colorectal metastatic cancer” and Dr. Ibane Abasolo, Scientific Coordinator of the same Unit, will participate with a talk titled “Extracellular vesicles increase the efficacy of Enzyme Replacement Therapy in Lysosomal Storage Disorders”.

The Virtual Lounge will be available as from October 21, 2020.

Registration Link for CLINAM SUMMIT 12 / 2020 (click here)

The final program: Download)

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