VisiMetrix: Gene reporter in vivo systems for compound screening and for the monitoring of physiological and disease status

Dr E.L. Kaijzel

Summary

'Visimetrix is developing a biologically-relevant test for testing new drugs for animals and humans as to their operation and toxicity. To do so, Visimetrix is creating a device with which a number of reporter genes can be applied accurately to the skin of an anaesthetised animal, and that emit light when they react with a chemical. Based on the difference in light intensities of the reporter genes, we can deduce the possible effect of the chemical to be tested. In doing so, Visimetrix is replacing the traditional testing method, which uses cells in bottles, by a more biologically-relevant model.’

4See Diagnostics: Empowering DNA Diagnostics

Dr W.L. de Laat

Summary

The last decade has seen ground-breaking progress in the analysis of human DNA. The genetic causes of many hereditary diseases have been identified and multiple personalised medicine tests have been successfully developed to match drugs to a patient’s genome and ensure that drugs are given only to patients who will benefit. However, all current genetic diagnostic assays miss frequently occurring mutations. 4See Diagnostics  have developed a new technology which can rapidly, affordably and accurately detect various sorts of genetic deviations missed by other approaches. In this project 4See Diagnostics are validating their technology in the analysis of various clinically relevant loci.
 

MicroLife Solutions (MLS): novel solutions for fungal infections and antibiotic resistance

Prof Dr A. Brouwer

MicroLife Solutions: new possibilities for combating viral infections and antibiotic resistance in plants

Summary

Around the world, plant disease results in a considerable loss of crops of around 20-40% per year. There are no effective means of combating many of the pathogenic microorganisms, or the methods available are based on applying chemical herbicides that, as a result of their environmental pollution and health risks, will soon be prohibited. There is also the growing issue of resistance in the use of chemical herbicides and the introduction of new plant diseases resulting from climate change. The estimated annual economic loss in reduced yield in crop production around the world is in the order of a few hundred billion Euros. The costs for using chemical herbicides to combat plant disease are around 25 billion Euros globally each year. As a result, there is an urgent need for developing new, effective antimicrobial products with few or no negative impact on the environment. The research team at MicroLife Solutions is working on this using the billions of soil bacteria that produce an almost inexhaustible source of new antimicrobial chemicals. Until recently, however, it was possible to only isolate some 3-5% of these soil bacteria, and the lion’s share could not be cultivated under laboratory conditions. The MLS team has developed a new, effective method, Metascreen™, for which we have applied for a patent, which makes it possible to isolate all soil bacteria and the antimicrobial products they generate. We have already discovered a new anti-fungal from the Collimonas soil bacteria.
The Pre-Seed Grant will be used to investigate the technical feasibility of Metascreen™ as well as the economic feasibility of producing new antimicrobial means for the Agro sector.

TCLASS: a new way of diagnosing cancer

Dr H. Lichtenbeld

Summary

At the moment, cancer is diagnosed by means of a lengthy and costly combination of hospital visits and investigation. Cancer metastasis throughout the body without finding the primary tumour is one of the types of cancer for which improved and faster diagnostics is urgently needed(*). TCLASS uses molecular chip technology that classifies tumour cells of metastases. The method determines the type of tumour with 90% accuracy, and thereby makes it possible to optimise the best personal treatment per patient.

(*) www.nytimes.com.

Therosteon: Developing innovative therapeutics for bone diseases

Prof Dr J.P.T.M. van Leeuwen

Summary

Osteoporosis is characterised by a loss of bone mass resulting from increasing bone decomposition that in turn leads to weaker bones and results in fractures, such as hip and/or vertebral fractures. The problem is that the bone loss cannot be diagnosed until the bone loss has occurred and that the current therapies are aimed at slowing down further bone loss and not at restoring the bone that has been lost. Therosteon is looking to develop therapies that stimulate bone formation and thereby restore the strength of the bones. Using the NGI Pre-Seed Grant, we will be looking to:
1) develop our main programme towards pre-clinical studies;
2) validate 2-3 new therapeutic pretexts we have identified;
3) optimise our strategy and business plan.

High Throughput Analysis of Intestinal Microbiota for Pharmaceutical Applications

Prof Dr W.M. de Vos

Summary

Our alimentary canal is colonised from birth by a dynamic community of microorganisms, previously known as microflora and nowadays called microbiota, which contributes to our wellbeing but also plays a role in disease. Using genomics-based methods, one can quickly gain an understanding of the composition and function of our intestinal microbiota. The objective of the new activities is to investigate the pharmaceutical applicants of these methods and to valorise. For further information please send an email to pharmabiota@cs.com

Diagnosis of Ischemic Heart Disease by use of specific RNA expression patterns in circulating progenitor cells in the blood

H.J. Duckers

Summary

Ischemic heart and vascular disease are the most common form of morbidity in the Western world as a result of the increasing age of the population and lifestyle (limited movement and high food intake). The variable and flighty character of the affliction interferes with an ad hoc diagnosis. Moreover, a clear diagnosis is only possible at the moment that there is actual ischemia (circulation disorder) with chest pains. The current diagnostic tools (such as the electrocardiogram (ECG) and exertion tests) are limited in their sensitivity and specificity and are not suitable for all target groups.

Using various in vivo models, we have been able to identify genes that are regulated in the natural reaction to ischemic heart and vascular disease. These genes can be used to diagnose a patient who has undergone an ischemic period or to check whether the therapy has achieved the intended effect (improved circulation in the heart). BioTxs aims to set up a test that analyses the gene profile of heart and vascular disease patients that can be used to identity these patients.

Swan Diagnostics: Test-to-tell; Development of over-the-counter home diagnostics tests

Dr J.H.L. Velthuis

Summary

Swan Diagnostics develops innovative diagnostic tests for home use. The first product FertiGO is a test for male fertility. Approximately one quarter of all couples who try to get pregnant struggle to do so. According to the World Health Organisation (WHO), male sperm has to have a certain amount of active sperm cells to be effective. In cooperation with academic hospitals and fertility centres, Swan Diagnostics is developing a test that shows easily and reliably whether the male is fertile. Based on this technical concept, Swan Diagnostics will be developing further home tests for new applications.

Commercial development of ubiquitinated peptides and screening assays produced by high throughput robotic peptide synthesis

Dr H. Ovaa

Summary

Ubiquitin is a small regulatory protein that controls many biological processes. Since this regulation is involved in many diseases, there is a strong interest in molecules which have been derived from ubiquitin. To satisfy this demand, the researchers will automate a recently developed technology to these so-called ubiquitin conjugates. In addition to the stimulation of research, this will also enable the development of novel and powerful screening-assays; an important step in the direction of new medicines.

XAir Diagnostics: metabolomics of exhaled air for the diagnosis and monitoring of inflammatory disorders

Prof dr F.J. van Schooten

Summary

Exhaled air contains thousands of volatile organic compounds (VOCs) that can be measured by mass spectrometry-based technologies. Pattern recognition provides unique VOC sets with high sensitivity and specificity that can be matched to diseases including inflammatory bowel disease (IBD). The pre-seed grant will be used to validate our diagnostic VOC profiles in a large group of IBD patients that will be followed for a year. Then, a start will be made to introduce the exhaled breath tests in the clinic. Xair Diagnostics BV will be established to assist the commercialization of the exhaled breath tests for chronic diseases based on the XVOC technology platform.

A monitor for mitochondrial function in the intensive care

Drs E.G. Mik

Summary

Mitochondria are the energy factories of our cells. They convert energy from nutrients into energy for the
cells by mitochondrial respiration, a process that uses oxygen. Adequate supply of oxygen to the mitochondria and a good function of these organelles is of vital importance. Recently, we developed a new technique that enables the measurement of oxygen tension in mitochondria (via oxygen dependent quenching of delayed fluorescence of protoporphyrine IX). Since the technique measures specifically in mitochondria this is also
a potential method for the measurement of mitochondrial function. The aim of this project is to use this technique to develop the first clinical monitor for mitochondrial function.

Development of a potent natural TLR4 antagonist as a new therapeutic drug against rheumatoid arthritis

Dr L.A.B. Joosten

Summary

Bacteria are recognized by specific receptors on immune cells. These Toll-like receptors (TLR) also play an important role in autoimmune diseases such as rheumatoid arthritis. Bartonella quintana LPS (Lipopolysaccharide) is an inhibitor of TLR4 and protects mice against inflammation. The goal of this project is to produce this TLR4 inhibitor for clinical applications.

Targeting the histamine H4 receptor: a new way to address unmet clinical needs by Griffin Discoveries

Prof dr R. Leurs, VU

Summary

A new generation of antihistamines? There is an increasing awareness that histamine receptor ligands, and especially ligands that are active on the histamine receptor subtypes H1R and H4R can play an important role in the treatment of pruritis (itch). Moreover, dual-action compounds that combine simultaneous blockade of the H1R and H4R in one molecule are believed to have superior efficacy against itch than either a H1R or
H4R antagonist given alone. In this project we will exploit our unique knowledge of histamine receptors to develop molecules with these activities and establish proof of concept by studying their efficacy in animal models of itch.

IS-pro: A molecular tool for clinical diagnostics of inflammatory bowel disease

Prof dr P.H.M. Savelkoul, Drs M.E. Grasman

Summary

DNA-test for rapid diagnosis of intestinal flora. The bacteria in the gut ensure that we can extract the correct nutrients from our food. Optimal composition of this intestinal flora is important and deviations cause chronic diseases. Little is known of intestinal flora because so far good diagnostics are not available. Scientists of the VUmc have developed a DNA test that makes it possible to show what exactly is wrong and what can be done, in a relatively simple and quick way. It is expected that the test will be available within 2 years.

Commercialisation of Enhanced Cell Proliferation Reactor (ECPR)for more cost-effective manufacturing procedures for cell therapy and/or tissueengineered products

Dr ing. A.J.M. Pemen

Summary

Large-scale cost-effective production of biological cells for cell-and tissue therapies is often difficult in practice, because many cells grow slowly and often only results in a limited amount of cells. Researchers of the Technische Universiteit Eindhoven (TU/e) have found that specific ultrafast high intensity electromagnetic fields have a strong growth stimulating effect. These fields have the unique ability to penetrate deep inside biological cells and to manipulate cell functions. This Pre-Seed Grant project aims to validate the technique, called ECPR (Enhanced cell proliferation Reactor,) and market it, in order to reduce the cost of cell culture.

Validation and implementation of the Multiple Array Probe Leiden (MAPLe) for diagnosis and treatment of pelvic floor dysfunction

Dr P.J. Voorham-van der Zalm

Summary

Scientific research has shown, that the current probes are not able to register the pelvic floor muscles accurately. For an optimal diagnosis and treatment of pelvic floor dysfunctions a standardized and validated probe is needed. The Department of Urology of the Leiden University Medical Center (LUMC) has developed a new probe, the Multiple Array Probe Leiden (MAPLe), that registers the EMG signals of the pelvic bottom in a better way. The LUMC has launched an investigation in order to validate the MAPLe and to determine normal values for the pelvic floor. The project is performed in collaboration with MAXAM Medical.

Mucosa: alternative testing for cosmetic and pharmaceutical industry

A.P. Vriens

Summary

New cosmetic products are currently tested on animals. This preclinical testing provides a risk assessment on factors such as irritation and cytotoxicity. In the period 2009 - 2013, the majority of tests conducted on animals to ensure safety of cosmetic products will be prohibited by the European Commission, with companies forced to use alternative methods. The aim of this project is to optimise and validate an alternative test method for risk assessment of oral products by using skin cell culture.

Development and refinement of a human stem cell based cardiac safety pharmacology assay

Dr R.C.J.J. Passier

Summary

There is a huge need for reliable pharmacological test models, which can identify potentially harmful side effects of medications, particularly for the heart, early on in the development process. Such a human test model would, apart from the increasing the safety of medications, dramatically reduce the costs and the time needed to bring medicines to the market. Human stem cells can, under the right circumstances, be differentiated into functional heart muscle cells. Recently, we have shown that heart muscle cells derived from human stem cells represent a good model for the testing of drugs on electrophysiological signals. Our goal is to optimize, standardize, and validate the production of human heart muscle cells for the large-scale testing of drugs with respect to harmful effects on the heart.

Khondrion: mitochondrial scientific services

Prof dr J.A.M. Smeitink

Summary

Energy, as produced by the cell's powerhouses - mitochondria - is essential for life. Disturbances in
the cell's energy production capacity is associated with many diseases and conditions like inborn
errors of metabolism, Parkinson and ageing. Khondrion's team aims to make a substantial contribution
to the development of a cure for mitochondrial disease and related disorders. Khondrion, thanks to its
strategic partnership with the expert centre the Nijmegen Centre for Mitochondrial Disorders at the
Radboud University Nijmegen Medical Centre, The Netherlands has access to all mitochondrial
technology. Khondrion offers to investigate small molecules and nutraceuticals on their potential to
modulate cellular energy metabolism by its life cell imaging multi-parameter read-out platform for the
food and pharma industry.

MyLife Technologies MicroNeedle Array for efficacious and painless delivery of active medical compounds in the skin

Dr Ing. R. Luttge

Summary

Administering vaccines is accompanied with many problems: pain at the injection site, the relatively large volume of foreign substances that is administered, and the risk of contaminated needles. Vaccine producers have been looking for alternative formulations to solve these problems for a long time. MyLife Technologies, a spin-off of the University of Twente is working on a solution. MyLife Technologies has developed a simple replication process for her new painless vaccine patch. The porous structure of the micro needles used, allows for a low and optimal dosage of active substances. Currently, a number of validation studies concerning this project are ongoing.

GlycoCheck: Check your health

Dr J.D. Jonge

Summary

GlycoCheck develops a non-invasive test for early detection of personal vascular vulnerability in the context of increased cardiovascular risk. The test is based on automated analysis of clinical videomicroscopic recordings of microvascular hemodynamics to check the quality of the endothelial glycocalyx, a protective coating on the luminal surface of blood vessels. An intact glycocalyx forms the first line of defence of blood vessels against atherogenic challenges by limiting leakage of atherogenic lipoproteins into the vessel wall and preventing adhesion of circulating coagulatory and inflammatory cells to the vascular endothelial lining. Recent preliminary clinical studies have demonstrated that monitoring glycocalyx damage identifies early vascular vulnerability before the onset of vascular disease.

Building the Lgr5/6 stem cell technology platform

Prof J.C. Clevers

Summary

We have recently identified two unique stem cell markers that have allowed us to visualize, isolate and culture known and novel stem cell types from a wide diversity of tissues and cancers. Long-term expansion in culture of tissue stem cells and the associated cancers has been established for stomach, small intestine, colon, pancreas and liver. The aim of this Pre-Seed Grant project is to develop the associated tools and technologies into a commercial platform for toxicology and therapeutic drug screening. Moreover, the current stem cell culture technology will be developed into a GLP/GMP-compatible procedure for potential in vivo regenerative medicine applications.

CriPec: Translation of a polymeric drug delivery platform into pharmaceutical products

Dr C.J.F. Rijcken

Summary

Cristal Delivery’s polymeric technologies (CriPec®) offer opportunities to develop drug products that strengthen effectiveness, offer improve a drug’s disposition, reduces side effects and easier dosing schedules for better compliance. In this project, a first actual drug product is being chosen and several preclinical studies will be performed. This will be done parallel to studies focused on the large scale production of the building blocks and nanoparticles under GMP-feasible conditions. Moreover, Cristal Delivery aims at expanding its technology platform and the applicability of CriPec® to different therapeutic agents, other routes of administration and a variety of diseases, partially in collaboration with academic and corporate partners.

Biomimiq: Your partner in human skin models for drug development

Dr ing. A. El Ghalbzouri

Summary

Preclinical drug development for various skin diseases including skin cancer, skin infections and eczema is hampered by the absence of representative and commercially available in vitro models for these diseases. In addition, animal testing is limited, the use of animals in cosmetic testing is banned starting in 2009, and a complete sales ban will be effective in 2013. Biomimiq offers a solution to this unmet need with its proprietary, unique and customizable in vitro human skin models representing both healthy and diseased human skin, ascertaining the company as one of the leaders in a large and rapidly growing market. In this Pre-Seed project, Biomimiq will finalize its strategic and business plans and professionalize its contract research activities in order to develop the company to a stage attractive to investors.

Hy2Care: Injectable hydrogels for cartilage repair

Dr H.B.J. Karperien

Summary

Hy2Care B.V. is a spin off company from the University of Twente and aims to introduce the first cure for osteoarthritis in patient care. Osteoarthritis is one of the most common degenerative joint disease that leads to damage of the cartilage surface. Hy2Care develops a so called “healing plaster” to repair the cartilage surface. The “healing plaster” is injected during an arthroscopic surgery on the cartilage surface. The “plaster” helps to calm the wound and following the repair of the cartilage. The Pre- Seed Grant enables Hy2Care to test the concept of the “healing plaster” in horses with cartilage damage. After this project patient studies will be started.

SCREVO: Cell and Tissue 3D High-throughput screening in vitro and in vivo

Dr ir. G.A. Higuera

Summary

There is growing evidence showing that three-dimensional (3D) culture systems better represent a physiological environment. The physiological environment created by 3D culture systems facilitate more accurate responses to newly developed treatments or more generally administered chemical compounds than conventional two-dimensional culture substrates. Screvo B.V. has developed proprietary 3D high-throughput screening systems for a broad range of in vitro and in vivo research. Screvo’s proprietary technology offers an opportunity to improve the output of preclinical research, while decreasing the social and economic impact of animal experimentation.

Targeted Nanoparticle Photodynamic Therapy

Dr D.J. Robinson

Summary

Targeted chemotherapy gives less primary side effects due to direct targeting of tumorcells. However, secondary side effects occur when the agent is metabolised and its cytotoxic components damage organs such as the liver and kidneys. This can be prevented by using targeted-nanoparticles-conjugates loaded with high concentrations of photosentisisers. These conjugates are cytotoxic only after exposure to therapeutic light. Together with Amrita Nanoscience Centre, India, targeted-nanoparticles-conjugates loaded with light sensitive compounds are developed which are specific and effective. This Pre-Seed Grant project aims at the production of different conjugates, investigation of pharmacokinetics in several tumor models, improving the efficiency of targeting and toxicology testing.

QVQ Quite Visible Quality (in antibodies)

Dr M. El Khattabi

Summary

Detection of diseases at an early stage will significantly contribute to an affordable health care. This will be realized by an in-house developed technology, wherein llama antibodies will be labeled to allow accurate imaging of diseases. To come to a successful business development, we will closely collaborate with top scientists across the world as well as with companies experienced in antibody-production. The currently funded NGI-project will lead to at least ten labeled antibodies (VHHs) that can aid in the early diagnosis of important diseases, such as cancer and cardiovascular diseases.

Waste2Chemical

Dr Ir. K.J.J. Steinbusch

Summary

Imagine that your apple core can be reused as biochemicals in paint, plastic or other applications. Recently,
at Wageningen University was discovered that the biochemicals, so called medium chain fatty acids, could be produced via a stable and fast mixed culture fermentation from organic waste materials. The use of low grade material as substrate results in a more sustainable and cheaper product, whereas the use of non−sterile conditions results in less expensive equipment and therefore lower investment costs. The research objective is to further develop the technology to such a high productivity level and efficiency that it is suitable for industrial application.

Braille4cells: design the surface that works best for you

Dr J. de Boer

Summary

Surface topography modification is an emerging topic in mayor applications as medical devices, anti-fouling and anti-bacterial surfaces. For example, in medical devices a grown concern is what surface topography improves implant performance and durability. Implant surface is the first thing its surroundings ‘sees’, and responds to. But how to design and select the optimal surface? Currently, it is common practice to screen manually maybe a dozen surface topographies based on trial-and-error. Materiomics offers their revolutionary proprietary TopoChip platform to screen much faster and efficiently thousands or even tens of thousands of surfaces at once to successfully find the optimal surface topography to elicit the desired biological response.

Tuba-scan: companion diagnostic for Chlamydia associated subfertility and tubal pathology

Dr S.A. Morré

Summary

Subfertility poses an enormous burden on healthcare since 15% of couples subfertility. Chlamydia trachomatis (CT) as most common cause of tubal pathology (TP) and subsequent infertility. Subfertile women get a CT serological test to decide who will get an invasive laparoscopy to assess TP (IVF candidates). Since 20% of the women CT- but havel TP and up to 45% of the women who are CT serology + do NOT have TP. TubaScan will add host genetic markers in relation to CT susceptibility and severity of infection to the serological testing to better identify women with TP without unneeded laparoscopies.

Ceronco: Enhancing drug membrane translocation in cancer treatment

Dr A. van Hell

Summary

Each cell in the body is enclosed by the plasma membrane, which is composed of lipids and proteins. This barrier prevents entry of harmful compounds. Anti-cancer therapy aims to kill tumour cells, and most cytostatic drugs only act after entering the tumour cell. Ceronco develops truncated lipid analogues that insert spontaneously in the plasma membrane and there facilitate the translocation of well-known cytostatic drugs, like doxorubicin. Thereby, more drug accumulates inside the tumour cell, while normal cells are spared. Ceronco is developing the technology towards more effective doxorubicin therapy in cancer patients.

ThromboDx: Diagnosing cancer from thrombocytes for personalized applications

Dr T. Wurdinger

Summary

The biochip platform: in-vivo whole embryo drug discovery and preclinical safety & side effects screening for pharmaceuticals and academia

Prof. dr Michael K. Richardson

Summary

Plant-e: living plants generate electricity

Ir. M. Helder

Summary

Platform for malaria drug discovery

Prof. dr Sauerwein

Summary