The list of national projects SAS

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Institute: Biomedical Research Center SAS

FP7 Health: Clinical Development of Nitisinone for Alkaptonuria
7RP Zdravie: Klinický vývoj Nitisinonu pre Alkaptonúriu
Program: FP7
Project leader: Mgr. Zaťková Andrea PhD.
Annotation:DevelopAKUre is a proposal to fund the clinical development of an orphan designated drug, nitisinone, for the treatment of a rare Mendelian disease, Alkaptonuria (AKU). AKU is a genetic deficiency of homogentisic acid dioxygenase, causing high levels of homogentisic acid (HGA). Oxidation of HGA to pigment polymer, termed ochronosis, alters connective tissues. This leads to multisystemic damage dominated by premature severe arthritis. Currently, multiple arthroplasty is inevitable since AKU is incurable and there is no effective palliative therapy. No data exists regarding the presence or absence of ochronosis before age 30 years. Hence, it is unknown whether treatment is necessary before then. A potential HGA-lowering therapy with nitisinone is available, but lacks outcome data. Thanks to our existing successful fundamental and clinical research (cell models, animal models, natural history studies), we are now ready for the final stage of clinical development of nitisinone for AKU in order to overcome these challenges. This will involve a dose finding study, a phase 3 clinical trial to prove efficacy, and a cross-sectional study in children and young adults to determine when to start treatment. The results of DevelopAKUre will allow us to make the case to the European Medicines Agency for marketing authorisation of nitisinone for AKU, thereby contributing to the goal of the International Rare Diseases Research Consortium of 200 new therapies by 2020. Our consortium has worked together for five years already. It includes Liverpool Universitys AKU Research Team as the lead applicant, the AKU Society UK patient group for dissemination and patient recruitment, three SMEs (Denmark, Netherlands) for biomarker analysis and clinical trial coordination, an industry partner (Sweden) supplying the drug and regulatory support, three universities (UK, Italy, Slovakia) for the analysis of data, and three clinical trial centres (UK, France, Slovakia) to reach required numbers.
Duration: 1.11.2012 - 30.4.2018

Association of the hypoxia-induced carbonic anhydrase IX with drug response, miRNA profile and oncogenic pathways: from integrative analysis of the NCI60 cancer cell panel to cancer patients
Asociácia hypoxiou-indukovanej karbonickej anhydrázy IX s odpoveďou na liečbu, s mikro-RNA profilom a onkogénnymi dráhami: od integrovanej analýzy NCI60 panelu nádorových buniek k pacientom
Program: Inter-academic agreement
Project leader: prof. RNDr. Pastoreková Silvia DrSc.
Annotation:Hypoxia frequently occurs in solid tumors, where it drives cancer progression and therapy resistance through activation of pro-survival and pro-metastatic molecules, including carbonic anhydrase IX (CA IX). This project aims to better understand the CA IX value in predicting metastasis and therapy response and identify oncogenic pathways that regulate or crosstalk with CA IX. We will use a well-established NCI60 cell lines of 9 tumor types, for which large datasets of genomic, proteomic, metabolomic and micro-RNA data exist in public databases. Preliminary analyses showed relationships of the normoxic CA IX levels to expression of the miR-200 family (involved in metastasis) and to some FDA-approved anticancer drugs. Since CA IX is induced by hypoxia and data from hypoxic NCI60 panel are limited, we will assess hypoxic CA IX expression levels and micro-RNA profile. This will allow us to obtain original data on hypoxia-related oncogenic pathways and pharmacogenomic correlates. The data will be validated by manipulating expression of CA IX and other selected molecules, and by analysis of tumor tissues. The partners will benefit from complementary skills. The SAS partner is experienced in research of tumor hypoxia and CA IX (being a leading authority in this field), the MOST partner has experiences in the work with NCI60 panel, miRNA profiling, pharmacogenomics and bioinformatics. The expected outputs include common publications and data potentially applicable to clinic.
Duration: 1.1.2015 - 31.12.2017

Effects of vortioxetine in the tryptophan-depletion model of SSRI-resistant depression in female rats
Efekt vortioxetínu v SSRI-rezistentom modeli depresie založenom na tryptofánovej deplécii u samíc potkanov
Program: Other
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.7.2014 - 31.12.2018

European virus archive goes global.
Európsky vírusový archív sa stáva globálnym.
Program: Horizon 2020
Project leader: RNDr. Klempa Boris DrSc.
Duration: 1.4.2015 - 31.3.2019

Innovative Nanopharmaceuticals: Targeting Breast Cancer Stem Cells by a Novel Combination of Epigenetic and Anticancer Drugs with Gene Therapy
Inovatívne nanoliečivá: Nová kombinácia epigentických a protinádorových liečiv s génovou terapiou zacielená voči nádorovým kmeňovým bunkám karcinómu prsníka
Program: ERANET
Project leader: Mgr. Kučerová Lucia PhD.
Annotation:The aim of the INNOCENT project is to develop innovative multifunctional nanopharmaceuticals to overcome the low efficacy and frequent relapses in breast cancer (BC) treatment, with emphasis on cancer stem cells (CSCs). The proposed multimodal COMBOBOMB, brilliantly integrates the diagnostic and therapeutic functions within a single nanostructure. The COMBOBOMB harbours four major components: 1) a selective targeting moiety (chitosan-targeted CD44); 2) a diagnostic imaging aid for localization of the malignant tumour and its micro- or macrometastases (inorganic nanocrystals); 3) a cytotoxic drug (doxorubicin), and 4) a chemosensitising agent (decitabine, DAC along with DAC-activating enzyme) utilising gene therapy and epigenetic approaches.
Duration: 1.1.2017 - 31.12.2019

Multiple myeloma intra-clonal heterogeneity: evolution and implications of targeted therapy
Intraklonálna heterogenita v mnohopočetnom myelóme: evolúcia a implikácie pre cielenú liečbu
Program: ERANET
Project leader: RNDr. Jakubíková Jana PhD.
Annotation:The overall objective of this proposal is to investigate evolution of intra-clonal heterogeneity during the development and progression of MM by combining cellular, molecular, and genetic approaches. Moreover, defining the impact of chemotherapy and/or immunotherapy on intra-clonal selection, together with the role of the tumor microenvironment on clonal dynamics on the level of genetic and cellular complexity, will provide the framework for development of novel personalized diagnostic criteria that will lead to more effective therapeutic strategies. Our emphasize will focus on the process of clonal evolution during the development of MM: from premalignant precursor conditions known as MGUS and smoldering MM without clinical manifestations of diseases but with present cytogenetic and/or gene-expression abnormalities to active disease stages. Moreover, we will evaluate the impact of novel chemotherapy/immunotherapy on the dynamic nature of the clonal selection in MM in our ongoing clinical trials, either alone or together with other conventional anti-MM therapies, delineating their ability to prevent recurrence of subclones and resistance to therapy. Furthermore, the role of the tumor microenvironment by characterizing the impact of overall host immunity on clonal selection will be defined.
Duration: 1.7.2016 - 30.6.2019

The Comet assay as a human biomonitoring tool
Kométový test ako nástroj na biologické monitorovanie ľudí
Program: COST
Project leader: RNDr. Gábelová Alena CSc.
Annotation:Many human biomonitoring studies have used the comet assay to measure DNA damage (some also measuring DNA repair). In most cases, the assay is applied to peripheral blood mononuclear cells. Results from relatively small individual studies are often inconsistent, and it is advantageous to carry out a pooled analysis of the combined data from all available studies. hCOMET will be a network comprising researchers who are active (or intend to be active) in human biomonitoring with this assay. Results supplied by these researchers will be compiled as a single database representing an estimated 19,000 individual DNA damage measurements. The pooled analysis will allow us to determine which factors (smoking, age, nutrition, sex, occupational exposure etc.) affect DNA damage, and to what extent. Fewer studies have included DNA repair capacity as an endpoint; we will collect what data we can and carry out a detailed review (or a pooled analysis if enough data). In addition, hCOMET will address the issue of inter-laboratory reproducibility of the assay by devising standard protocols, for both DNA damage and DNA repair measurement, coordinating ring studies to test these protocols, and offering training courses and exchanges, so that in future comparison of results from different studies will be facilitated. We will review applications of the assay to other human cell types and isolation methods (such as leukocytes obtained from frozen blood).
Duration: 1.4.2016 - 31.3.2020

Lipidized analogs of prolactin-releasing peptide (PrRP): Immunohistochemical evaluation of their central effects
Lipidované analógy prolaktín-uvoľnujúceho peptidu (PrRP): imunohistochemické hodnotenie ich centrálneho účinku
Program: Bilateral - other
Project leader: doc. PharmDr. Pirník Zdenko PhD.
Duration: 1.4.2014 - 31.12.2017

MEchanisms of Lymphocytes TRansmigration Across the Blood Brain Barrier; NEURON ERA Net ll)
MEchanizmy TRansmigrácie Lymfocytov cez Hematoencefalickú Bariéru; NEURON ERA Net IId Brain Barrier; NEURON ERA Net II
Program: ERANET
Project leader: MUDr. Penesová Adela PhD.
Annotation:We are members of NEURON ERA Net II consortium, where all are specialists in inflammatory processes of the central nervous system (CNS) in general and multiple sclerosis research in particular. The highly complex pathogenesis of many neuroinflammatory diseases, such as multiple sclerosis (MS) clearly includes a significant vascular and inflammatory component (Minagar et al 2012). The aim of our work package (WP) is to investigate in vivo immune and endothelial microparticles (MP) in cerebrospinal fluid (CSF) and plasma as well as plasma levels of developmental endothelial locus 1 (Del-1) from the samples of patients with neuroinflammatory diseases versus non-inflammatory diseases and their importance as a biomarkers of disease activity and as predictor marker of the response to biological treatment. The overarching goal of this WP is to identify novel biomarkers that could be used to design very specific and efficient therapies to treat neuroinflammatory diseases. We expect that MP can be a powerful biomarker of MS disease activity, disease progression and predictive marker of response to treatment.
Duration: 1.8.2015 - 31.7.2018

Skeletal muscle metabolic abnormalities in patients with idiopathic inflammatory myopathies
Metabolické abnormality kostrového svalu u pacientov s idiopatickými zápalovými myopatiami
Program: Bilateral - other
Project leader: doc. MUDr. Ukropcová Barbara PhD.
Duration: 1.4.2016 - 31.3.2020

Anti-tick Vaccines to Prevent Tick-borne Diseases in Europe
Proti-kliešťové vakcíny na prevenciu kliešťami prenášaných ochorení v Európe
Program: FP7
Project leader: RNDr. Klempa Boris DrSc.
Annotation:Ixodes ricinus transmits bacterial, protozoal and viral pathogens that cause Lyme borreliosis, babesiosis and tick-borne encephalitis respectively and exceedingly affect Central and Eastern Europe. Anti-tick vaccines encompass an innovative strategy to prevent tick-borne diseases (TBDs) in humans, or animals and wildlife to indirectly reduce the risk of contracting TBDs for humans. Overall objective of the project is to identify and characterize tick proteins involved in ‘tick immunity’ and TBP transmission and to use this knowledge to develop anti-tick vaccines to prevent multiple human TBDs. Using state of the art proteomic and transcriptomic approaches we will identify and characterize novel tick salivary gland proteins, which will be subsequently assessed as anti-tick vaccines to protect against LB, babesiosis and TBE in animal models. In addition, through an integrated and multidisciplinary approach involving public health institutes, health organizations and industrial companies we will examine how to develop anti-tick vaccines and implement these in public health systems.
Duration: 1.12.2013 - 30.11.2018

Antitumour effect of trialkyl- and triaryltin compounds, biologically active ligands of nuclear retinoid X receptors in human breast cancer cell lines
Protinádorový účinok trialkyl- a triarylcínových zlúčenín, biologicky aktivnych ligandov nukleárnych retinoidných X receptorov v ľudských nádorových liniach karcinómu prsníka
Program: Inter-academic agreement
Project leader: Ing. Brtko Július DrSc.
Duration: 1.1.2015 - 31.12.2017

Vesicular glutamate transporter 3 knockout mice and changes in gene expression of the transporter: relation to stress hormones, behavior and animal models of mood disorders
Vezikulárny glutamátový transportér a zmeny v jeho génovej expresii: vzťah k stresovým hormónom, správaniu a animálnym modelom psychických porúch
Program: Bilateral - other
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.1.2016 - 31.12.2018

High level Integrated Sensor for Nano Toxicity Screening
Vysokointegrovany senzor na skrining nanotoxicity
Program: Horizon 2020
Project leader: RNDr. Gábelová Alena CSc.
Annotation:The HISENTS vision is to address the problem of the dearth of high-quality tools for nano-safety assessment by introducing an innovative multimodular high throughput screening (HTP) platform including a set of individual modules each representing a critical physiological function connected and integrated in a hierarchical vectorial manner by a microfluidic network. The increase of the capacity to perform nano-safety assessment will be realised by innovative instrumentation developments for HTP and high content analysis (HCA) approaches. Toxicogenomics on chip is also one embedded objective. Our interdisciplinary approach focuses on tools to maximise the read-across and to assess applicable endpoints for advanced risk assessment of nanomaterials (NM). The main goal is thus to establish individual chip-based microfluidic tools as devices for (nano)toxicity screening which can be combined as an online HTP platform. Seven different chip-based sensor elements will be developed and hierarchically combined via a flow system to characterise toxicity pathways of NM. The HISENTS platform allows the grouping and identifying of NM. Parallel to the screening, the pathway and interaction of NM in biological organisms will be simulated using the physiologically based pharmacokinetic (PBPK) model. Using the different sensor modules from the molecular to cell to organ level, HISENTS can input quantitative parameters into the PBPK model resulting in an effective pathway analysis for NM and other critical compounds. The developed platform is crucial for realistic nano-safety assessment and will also find extensive application in pharmaceutical screening due to the flexible modifications of the HTP platform. The specific objective is the development of a multimodular HTP platform as new a screening tool for enhancing the efficiency of hazard profiling. Currently, no such flexible, easy-to-use screening platform with flexibly combinable chip-based sensors is available on the market.
Duration: 1.4.2016 - 31.3.2019

Application of next generation sequencing for the study and diagnosis of plant viral diseases in agriculture
Využitie sekvenovania novej generácie pre štúdium a diagnostiku vírusových chorôb rastlín v poľnohospodárstve
Program: COST
Project leader: Ing. Glasa Miroslav PhD.
Duration: 9.3.2015 - 8.3.2019

Development of galectin-based therapeutics for the treatment of hantaviral hemorrhagic fever
Vývoj na galektínoch postavených terapeutík pre liečbu hantavírusovej hemoragickej horúčky
Program: ERANET
Project leader: RNDr. Klempa Boris DrSc.
Duration: 1.1.2016 - 31.12.2017

Relationship between basal metabolism and regulation of endocytosis and apocrine secretion in Drosophila salivary glands.
Vzťah medzi bazálnym metabolizmom a reguláciou endocytózy a apokrinnej sekrécie v slinných žľazách Drosophila melanogaster.
Program: Inter-academic agreement
Project leader: RNDr. Farkaš Robert CSc.
Annotation:Basal or overall metabolism of the ogranism is reflected in the respiratory activity of mitochondria that can be monitored as consumption of oxygen and/or release of carbon dioxide. In the past, experimental or diagnostic measurement of the respiration was limited to whole organism and was able to provide only coarse data. However, respiratory activity and responses of individual tissues or groups of cells which would potentially respond differently could not be monitored due to limited sensitivity of respirographs. During last two decades there was significant development and improvements in the microrespirographic methods that are sensitive enough to measure nanoliter changes in the volume of oxygen consumption that corresponds to the capacity of small tissues or few hundred cells isolated from model organisms such as Drosophila. Recently discovered tremendous endocytosis and massive apocrine secretion in Drosophila opened new possibility to find a link between developmentally-associated metabolic changes and group of genes regulating endocytosis and subsequent apocrine secretion.
Duration: 1.1.2015 - 31.12.2017

Relationship between changes of oxytocin levels and brain development
Vzťah medzi zmenami hladín oxytocínu a vývinom mozgu
Program: Inter-academic agreement
Project leader: RNDr. Bakoš Ján PhD.
Duration: 1.1.2016 - 31.12.2018

Developing a rat model of depression based on tryptophan deficiency
Zavedenie animálneho modelu depresie založenom na tryptofanovej deplécii
Program: Bilateral - other
Project leader: prof. PharmDr. Ježová Daniela DrSc.
Duration: 1.5.2011 - 31.12.2017

The total number of projects: 19