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Luxembourg hosts international flagship cancer epidemiology conference

Bringing together about 150 international scientists, clinicians, healthcare professionals and policymakers from 17 nations, the 45th edition of the Group of Cancer Epidemiology and Registration in Latin Language Countries (GRELL) conference takes place in Luxembourg in a fully virtual format.

Organised in Luxembourg for the first time by the National Cancer Registry of Luxembourg (RNC) at the Luxembourg Institute of Health (LIH), the meeting features several prominent speakers, providing an opportunity to discuss the latest developments in the field of
cancer epidemiology with a particular focus on COVID-19 and cancer, as well as childhood and adolescent cancers.

National and international prominent speakers in Luxembourg

The three-day event gathers prominent speakers, who are addressing some of the key clinical challenges related to cancer.

Some of the national and international speakers and moderators include:

The association aims to coordinate the activities of the “Group for Epidemiology and Cancer Registry in Latin Laguage Coutries” (GRELL), gathered since 1976.

GRELL promotes epidemiological cancer research, mainly through the registration of cases in geographically defined populations.

Visit Luxembourg Institute of Health to know more.

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Vocal Biomarkers: What our voice tells us about our health

A Research Luxembourg team has published an overview on the use of voice monitoring in Digital Health.

A voice reveals a lot about a person’s health: Does it sound strong? Does it sound weak? Is it hoarse? Are there indications of pain or fatigue? Modern digital technologies have recently made it possible to detect the smallest changes in the voice. But now, more research is needed to make the results of this voice monitoring usable for medical and diagnostic purposes.

©Michal Czyz / Unsplash

From research to clinical practice

To this end, a team at the Luxembourg Institute of Health (LIH) led by Dr. Guy Fagherazzi, director of the Department of Population Health and head of the Deep Digital Phenotyping Research Unit, has written a review on the topic of “vocal biomarkers”. In this paper, the research team describes the state of the art of voice analysis for health purposes and the evaluation of speech recordings with the help of artificial intelligence. The scientists have also described a pipeline in which the corresponding techniques can be coordinated and used for all the way up to medical applications. They have thus created an important basis for systematically advancing voice analysis in the field of digital health and making it ready for use in clinical practice. The publication “Voice For Health: The Use Of Vocal Biomarkers From Research To Clinical Practice” was published on April 16th in the journal “Digital Biomarkers“.  

In the age of analogue medicine, a person would go to the doctor when he or she felt unwell. The doctor would perform an examination, make a diagnosis and prescribe a treatment for the patient. Until the next visit to the doctor, there was a period during which no one knew the patient’s exact state of health. But times are changing, as Dr. Guy Fagherazzi says: “We can now also use digital technologies to monitor a patient’s condition between two visits to the doctor – and intervene if his or her condition should deteriorate.” According to Fagherazzi, a key to this is the human voice. “If a person’s state of health changes, this immediately affects the voice,” the scientist says. The changes may be barely perceptible to the human ear. But digital technologies and artificial intelligence can measurably detect them as useful markers for diagnostic and medical purposes.

Evaluating voice recordings with artificial intelligence

At LIH, this is an important new field of research. There are several projects addressing this topic, which hope to make digital voice analysis usable for combating COVID-19, among other things. “The first thing we did was to assess how far research in this field has already come,” says Fagherazzi. Together with his team and colleagues from the University of Luxembourg and the Luxembourg Institute of Science and Technology (LIST), he conducted a comprehensive literature review. The researchers learned which techniques are suitable for recording voices and how the data can be collected and stored. They compiled current methods for processing and evaluating voice recordings with the help of artificial intelligence, and identified which vocal biomarkers – which characteristics of the voice – can already be used to diagnose diseases and determine the state of health.

Describing the current health status is, however, only half the journey the LIH researchers decided to embark on. “We have also described in our paper how the different techniques need to be brought together and developed so that the use of vocal biomarkers becomes relevant for clinical practice,” Fagherazzi says.

“We will now be taking these steps into practice within the framework of various clinical projects running at LIH and its cooperation partners”

Several projects in the framework of the COVID-19

Two of these projects are related to COVID-19: in Predi-COVID, COVID-19 patients and their relatives are being systematically examined in order to identify biomarkers and risk factors associated with disease severity. In CDCVA, a project led by the University of Luxembourg and LIST in association with LIH, approaches are being researched to detect COVID-19 using cough and voice analyses. A third project, called CoLive Voice, will soon be launched to collect voice samples from volunteers all over the world. The goal of CoLive Voice is to advance voice-based diagnosis and symptom monitoring for a wide range of diseases, from cancer and diabetes to mental health and Parkinson’s disease.

Through all these projects, Fagherazzi hopes not only to gain new insights into digital voice monitoring, but also to ensure proximity to clinical practice:

“Vocal biomarkers will only become useful if we have this connection with clinics.”

For the future, he has three groups of key stakeholders in mind. The first is doctors who will be able to use voice analysis to monitor the condition and symptoms of their patients remotely, even when they are at home. The second is people who want to monitor their own current state of health using an app and voice samples. And the third group is pharmaceutical companies that can use the new techniques to capture better real-life data on the condition of their participants and on the tolerability and efficacy of new active substances in clinical trials. “We have now published a key paper,” Fagherazzi says. “But,” he adds with a wry smile, “more than anything else, the paper is the basis for a lot of work that now lies ahead of us”.  

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10 years building colorectal cancer collection in Luxembourg: an additional tool for translational research

The collection of tumour samples from various Luxembourg hospitals has enabled to launch several research projects, including European and international ones, which already present very promising results.

Initiated in 2011 by the University of Luxembourg and the Integrated Biobank of Luxembourg (IBBL) as a concerted action against colorectal cancer (CRC), the collection of tumour samples from various Luxembourg hospitals has enabled to launch several research projects which already present very promising results for the treatment of colorectal cancer patients.

Prof. Serge Haan and Dr. Elisabeth Letellier from the Department of Life Sciences and Medicine (DLSM) at the University of Luxembourg who launched the project in 2011 explain in more details the importance of such a collection.

Dr Elisabeth Letellier et Prof. Dr Serge Haan (Photo: University of Luxembourg)

How did the collection start?

In 2010, we gathered with Dr. Jos Even from the Laboratoire National de Santé (LNS) and the scientific management team from the IBBL to investigate colorectal cancer by setting up a high-quality tissue collection from colon cancer patients in Luxembourg. IBBL, in the context of its mission of serving the Luxembourg research community, decided to make this collection one of its strategic initiatives. The project started with the support of the Fondation Cancer and the Luxembourg National Research Fund (FNR).

Over the years, the collection has grown significantly with the launch of several research projects and the support of many partners such as the Laboratoire National de Santé (LNS), the Centre d’Investigation et d’Épidémiologie Clinique (CIEC/LIH), the Centre Hospitalier Emile Mayrisch (CHEM).

What is the current status of the collection?

Over the past years, we have established an ongoing collection of tumour tissue samples from CRC patients, assembling high quality samples of over 170 patients. This collection contains a multitude of sample types, such as serum, plasma, immune cells, stool and tumour tissue and normal counterparts from the same patients. Clinical parameters are available for all samples (age, gender, tumour location, survival, diet surveys, therapies, etc.), allowing for studies, which can generate highly valuable translational findings. Pre-analytical factors, such as the cold and warm ischemic time, the Bristol score, as well as dietary questionnaires are collected along with the samples.

We have a follow-up for these patients every year up to 5 years and clinical data is collected for more than 10 years. As the progression of CRC takes over 10 years, samples and data (survival, treatment etc.) covering 10 years are required to have a clinical relevant collection. This is why establishing such a cohort is a future-oriented project which will yield a lot of important translational findings in the domain of gastrointestinal cancers over the next years.

What is its value?

The collection allows generating results that can be translated into a clinical setting. Importantly, this cohort has a unique added value, based on (i) complete sets of sample types, (ii) full preanalytical documentation and characterisation, (iii) longitudinal follow-up samples, (iv) extended clinical data annotations, (v) quality control measurements. As we collect the tumour cells as well as the different cells of the tumour microenvironment, we can generate “small tumours” in the lab which nicely recapitulate the original tumour. These models allow us to study the mechanisms underlying tumour initiation as well as progression but also the development of novel drugs that not only target the tumour cells but also its microenvironment. This is crucial as the past years have clearly demonstrated that the tumour microenvironment plays a key role in tumour progression. Building up these complex tumour models from a patient’s material allows to develop drugs that are specific for this patient. In essence, it fosters personalised medicine.

Over the past years, we have acquired extensive knowledge in the exploitation of the results generated with the samples of the cohort. For example, by using our CRC cohort, we have identified promising biomarkers with a strong prognostic value in early CRC stages. One of our recently identified biomarkers has led to the filing of a patent on novel biomarkers for cancer diagnosis, prediction, or staging. Together with the IBBL, we obtained a Proof of Concept funding from the FNR to test one of the identified biomarkers for clinical use.

What is the future of the collection?

We have already initiated in collaboration with different groups at the University but also the Luxembourg Institute of Health (LIH) and international partners several research projects which are using the samples from the cohort or the cultures derived from them. As an example, IBBL was invited to join a European project, partly based on the value of our collection. These tools are important to generate high translational results. In addition, we have established a biobank at the University which contains 3D spheroid cultures, organoids, as well as cells of the tumour microenvironment such as fibroblasts. This biobank can be used by researchers to perform mechanistic studies as well as drug profiling or biomarker studies.

We would like to expand this cohort and involve more hospitals as for example the Hôpitaux Robert Schuman, Centre Hospitalier de Luxembourg and Centre Hospitalier du Nord. Our future aim is to include this cohort into the National Cancer Plan and further develop it as a national cohort that can be used by all researchers in Luxembourg and abroad.

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Launch of Cross-Europe nano-pharmaceutical project “PHOENIX” coordinated in Luxembourg

11 project partners from academia and industry located all across Europe have joined forces in a project called PHOENIX to create an “Open Innovation Test Bed” for nano-pharmaceuticals and it will all be coordinated in the Grand Duchy by Luxembourg Institute of Science and Technology (LIST).

PHOENIX is an innovation project funded by EU’s Horizon2020 Framework Programme and it aims to provide services for the development, characterisation, testing, safety assessment, scale-up, GMP production and commercialisation of nano-pharmaceuticals to the market, making them available to SMEs, start-ups, research laboratories and interested users.

The project is coordinated by Dr Tommaso Serchi at LIST and supported at MyBiotech near Saarbrücken for the Scientific Coordination by Dr Nazende Günday-Türeli. PHOENIX will have a duration of 48 months starting on 1 March 2021 with a total budget of €14.450 million and a requested EU contribution of €11.1 million.

What are nano-pharmaceuticals?

They are drugs that use nanotechnology (the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes) in some form. This could be in the sense that the drugs themselves are nanomaterials. For example, contrast agents are used in the form of nanoparticles rather than a molecule because nanoparticles are more stable and can stay longer in blood. Another example could be that the nanoparticle is used as a capsule to encapsulate the drug and protect it while enhancing adsorption and distribution.

Nano-pharmaceuticals have the potential to drive the scientific and technological uplift, offering great clinical and socioeconomic benefits to society in general, industry, key stakeholders and patients. Nevertheless, affordable and advanced testing, manufacturing facilities and services for novel nano-pharmaceuticals are main prerequisites for successful implementation of these advances to further enhance the growth and innovation capacity.

The implementation of an Open Innovation Test Bed

The establishment of current good manufacturing practice (cGMP) in nano-pharmaceutical production on a large scale is the key step to successfully transferring nano-pharmaceuticals from bench to bedside (from lab to industrial scale). Due to the lack of resources to implement GMP manufacturing at site, the upscaling and production of innovative nano-pharmaceuticals is still challenging to main players of EU nanomedicine market, start-ups and SMEs. To allow successful implementation of the nano-pharmaceuticals in the nanomedicine field, there is an urgent need to establish a science and regulatory-based Open Innovation Test Bed (OITB).

The PHOENIX project aims to enable the seamless, timely and cost-friendly transfer of nano-pharmaceuticals from lab bench to clinical trials by providing the necessary advanced, affordable and easily accessible PHOENIX -OITB which will offer a consolidated network of facilities, technologies, services and expertise for all the technology transfer aspects from characterisation, testing, verification up to scale up, GMP compliant manufacturing and regulatory guidance.

PHOENIX-OITB will develop and establish new facilities and upgrade existing ones to make them available to SMEs, starts-up and research laboratories for scale-up, GMP production and testing of nano-pharmaceuticals. The services and expertise provided by the OITB will include production and characterisation under GMP conditions, safety evaluation, regulatory compliance and commercialisation boost.

The 11 partners that form the PHOENIX consortium

  • Luxembourg Institute of Science and Technology (LIST) – Research and Technology Organisation (RTO) from Luxembourg – Project coordinator.
  • MyBiotech – Small Medium Enterprise (SME) from Germany – Project Scientific Coordinator.
  • Nanomol Technologies SL, SME from Spain.
  • LeanBio SL, SME from Spain.
  • BioNanoNet Forschungsgesellschaft mbH (BNN) – RTO from Austria.
  • Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC – two distinct institutes take part in the action CSIC-INMA and CSIC-ICMAB) – RTO from Spain.
  • Institute for Medical Research and Occupational Health (IMROH) – RTO from Croatia.
  • Research Center Pharmaceutical Engineering GmbH (RCPE) – RTO from Austria.
  • Cenya Imaging B.V. – SME from The Netherlands
  • Topas Therapeutics GmbH – Industry from Germany
  • Grace Bio SL – SME from Spain

More information on the project on LIST’s website

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Luxembourg to open healthtech incubator

Luxembourg’s new business health technologies incubator will open in spring 2021. Hosted at the House of Biohealth in Esch-Belval, it will offer 350 m2 of laboratory space to start-ups and spin-offs during their first 2-3 years of operation.

The opening of the new healthtech incubator was announced by Minister of the Economy Franz Fayot on 21 January 2021. “The health technology sector is a pillar of our economic diversification strategy,” said the minister. “Offering suitable infrastructure for hosting relevant companies in the healthtech sector is an asset in terms of attractiveness and sustainability for the national economic ecosystem.”

Accelerating economic impact

The health technologies incubator will contribute to accelerating the economic impact of investments made to develop public research in biomedicine in Luxembourg. In addition to fully equipped laboratories, hosted companies will also be able to benefit from professional support in the field of business development.

The incubator is part of the House of Biohealth, a hosting facility with office and lab space for both established companies and start-ups in the fields of biotech, cleantech and ICT. The House of Biohealth currently hosts 9 companies and two public research laboratories that are part of the Luxembourg Institute of Health (LIH) and the Luxembourg Centre for Systems Biomedicine (LCSB). Around 450 people work in various areas such as diagnostics, medical devices and digital health.

Once the healthtech incubator has been opened, the House of Biohealth with be able to host up to 600 researchers on close to 9,500 m2 of laboratory surface and 5,500 m2 of office space.

House of BioHealth in Esch-sur-Alzette ©House of BioHealth

“The House of Biohealth will be able to respond even better to the specific needs of start-ups and spin-offs, which can benefit from specific support to move successfully from the world of research to the world of business.”

Employment and investments in Research, Development and Innovation (RDI) are growing steadily.

Close to 5,000 highly qualified individuals are employed in research and development. This is equivalent to 13,4 persons per 1000 jobs. Another unique feature of Luxembourg’s economic landscape is the high percentage of service-based companies that are actively pursuing RDI activities. Indeed, more than 65% of service-based companies are involved in research, development and innovation activities (the average across sectors being 65%), whereas the share of industrial companies is 63%.

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Luxembourg: a leading location for Parkinson’s research

Over the past two decades, Luxembourg has developed into an internationally recognised hub for science. An important driving force behind this development is Parkinson’s research. The Grand Duchy is now one of the leading locations for this field of research. This can be attributed in part to the FNR-sponsored project NCER-PD, the National Centre for Excellence in Research on Parkinson’s Disease. NCER-PD is so successful that, in 2019, the FNR gave the green light and six million euros for the second funding period.

This article was originally published by the Luxembourg National Research Fund

Parkinson’s is a disease of the nervous system, characterised by the premature aging of brain cells that produce the chemical messenger dopamine. Among other things, dopamine controls motor function, and thus the targeted and voluntary movement of arms, legs and other parts of the body. Parkinson’s patients therefore tend to lose the proper coordination of their movements, which also become slow. They can have difficulty swallowing. The ability to make facial expressions diminishes. Many Parkinson’s patients develop tremors, the muscle shaking characteristic of the disease. Their sense of smell and sleep patterns can also be disrupted.

Not all Parkinson’s cases are the same

The symptoms of Parkinson’s disease are highly diverse and differ from one person to another.

“We now know that not all Parkinson’s cases are the same,” says Prof. Rejko Krüger, the coordinator of NCER-PD, referring to the many symptoms of this disease. “It has become clear that we are dealing with not only different constellations of symptoms, but also different causes and many different triggers of Parkinson’s as well.”

These can be genetic risk factors or certain environmental influences, for example. In a small percentage of Parkinson’s patients, the disease can be traced back to mutations in a single gene. Researchers have so far identified 20 genes whose mutations can lead to Parkinson’s.

Research for earlier diagnosis and better treatment

There is still no cure for Parkinson’s, nor is there any way to prevent or stop the disease. Yet, there are drugs and other therapeutic methods that can treat its symptoms well enough for many patients to live for many years with the disease. NCER-PD is helping to continually improve the treatment of symptoms, but the most important goal for the researchers is to find ways to treat Parkinson’s at its root.

NCER-PD is centred around a so-called patient cohort: a group of people who have consented to have their state of health regularly monitored by specialists over the span of many years. The participants give samples of body fluids such as blood or urine. They also take part in clinical examinations that analyse movement sequences and test their attention, memory, vision, speech and sense of smell.

1600 participants in the cohort

The cohort includes people with and without Parkinson’s disease. The regularity of the comprehensive examinations allows the researchers to obtain a precise overview of how each volunteer’s health status develops over time. From this, they aim to identify early warning signs to help diagnose Parkinson’s disease in its early stages, even before symptoms appear. They are studying, with scientific rigour, the long-term effects of certain treatments on the health of Parkinson’s patients. They are also learning what might be effective preventive measures.

The NCER-PD team and its many partners from Luxembourg’s research, clinical and ambulatory care sectors have been recruiting volunteers for the cohort since 2015, with great success. At the end of 2019, more than 800 patients and just as many healthy people had already given their consent. “We need these numbers,” says Krüger, “to ensure we can make representative and scientifically valid statements.”

Prof. Rejko Krüger ©scienceRELATIONS
Excellent review of outstanding scientific results

The monitoring of the cohort lays the foundation for the scientific work of the NCER-PD researchers and the publication of their results in respected scientific journals. NCER-PD’s track record is outstanding, as evidenced by an excellent rating from an international review panel last year. As a result, the Fonds National de la Recherche is providing another six million euros for NCER-PD until 2023.

This funding will allow the regular check-ups to continue for registered participants and to be offered to newly diagnosed patients as well. “We are furthermore planning two new risk cohorts,” says Krüger: “With them, we want to identify early symptoms of future Parkinson’s cases so that we can take preventive action when it is needed.”

Recognising early symptoms for prevention

The researchers already have the first clues as to what could be early signs; now they want to increase the level of confidence. They are looking for volunteers who have a specific sleep disorder, namely REM sleep behaviour disorder. These people talk or shout loudly in their sleep, sometimes also kicking and punching so harshly that even their partners suffer.

People with REM sleep behaviour disorder have a higher likelihood of developing Parkinson’s disease later in life. With the help of this first risk cohort, the NCER-PD researchers now want to gain a better understanding of this correlation.

For the second risk cohort, the scientists are approaching people who have a very specific mutation in the “GBA” gene. Every third person with a mutated GBA gene develops Parkinson’s disease. In the new study, the participants will be offered tests using MRI scans. This non-invasive imaging method allows researchers to visualise structural changes in the brain.

“We want to find out whether such changes already exist in people with the GBA mutation before Parkinson’s symptoms appear,” Krüger explains. “These would be very good early warning signs that would indicate the need for early therapy, and would thus clear new paths towards prevention.”

Researchers from NCER-PD were already are able to find early indicators of Parkinson’s disease using biochemical and mathematical methods. In cooperation with Saarland University, they identified molecules in blood samples from Parkinson’s patients that indicate the disease at a very early stage. These are called biomarkers.

“We already have many biomarkers in sight,” Rejko Krüger reports: “Now we are narrowing the list of potential molecules down to those candidates that can actually be used in future clinical diagnoses.”

Treatment methods in focus

During the second funding period of NCER-PD, the Parkinson’s researchers want in particular to make significant progress in the treatment of the disease. An important part of this will be clinical trials in vitro: new active substances will be tested in the laboratory on cells derived from tissue samples provided by patients who have a specific genetic predisposition to Parkinson’s disease. Promising substances from these experiments will then be developed further in clinical trials, with the aim of making them safe and effective for use in clinical practice.

Prof. Krüger underlines the importance of teamwork and thanks everyone involved for the results achieved so far: “NCER-PD’s success is based on the fact that, in Luxembourg, people from different institutions are collaborating in a spirit of strong mutual trust. Furthermore, we have a scientific infrastructure that meets the highest standards. This means we have a great opportunity in Luxembourg to lay the foundations for personalised, tailored Parkinson’s therapies.”

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A first interinstitutional research platform for translational research

The University of Luxembourg and the Luxembourg Institute of Health (LIH) have created a first inter-institutional research platform: the Disease Modelling Screening Platform (DMSP), a core facility for translational research.

The COVID-19 pandemic has shown that conducting strong translational research is key to combating the coronavirus. By leveraging cutting edge laboratory techniques to study patient samples, translational research quickly pivots laboratory discoveries into new therapies for patients, in a process known as the bench-to-bedside approach. Luxembourg has established excellent transversal and translational research, spanning several research topics and disease areas and integrating the results to provide holistic and meaningful insights that can tangibly improve clinical outcomes for patients. 

In this context, the University of Luxembourg and the Luxembourg Institute of Health (LIH) have created a first inter-institutional research platform: the Disease Modelling Screening Platform (DMSP), a core facility for translational research. The platform is one of the instruments of the recently signed bilateral agreement between the University and LIH to cooperate through participation in joint research projects and programmes, the development of common research platforms, the creation of inter-institutional research groups and the collaboration in doctoral education.

Laboratories at the University of Luxembourg (Photo: ©Laurent Antonelli/Blitz Agency)

The highly translational dimension and purpose of DMSP are fully reflected in its governance and staff composition, which leverage the expertise of the Luxembourg Centre for Systems Biomedicine (LCSB) on the one hand, and of LIH’s Personalised Drug Discovery research group and Transversal Translational Medicine (TTM) on the other. DMSP is currently led by Dr Yong-Jun Kwon (LIH), Head of the Early Drug Discovery Platform of the Personalized Drug Discovery unit, who supervises the implementation of several drug screening programmes on the LIH side, while Prof Dr Rejko Krüger, joint professor for Neuroscience at the University and Director of TTM at LIH, has been involved in the platform since its early conception.    

Indeed, the origin of the platform dates back to 2014, when Prof. Krüger joined the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg with an FNR PEARL grant and a mission to bridge clinical patient care and basic research, and ultimately improve our understanding of Parkinson’s Disease. The original idea was to create a more patient-centered approach and use patient-derived cellular models that were established in the labs to develop new treatments for Parkinson’s Disease in the future. An automation platform, established in 2016, applied a specific cell screening technique to discover neuroprotective compounds as part of repurposing already approved drugs.

Today, the ambition of the LIH-University collaboration on the DSMP is to make translational research sustainable. In line with the transversal and translational vision, the DSMP is no longer limited to Parkinson’s Disease. Indeed, it will also support research projects on a variety of different disease areas, such as cancer and pain therapy. The close interinstitutional partnership and trust between LIH and the University thus ensure the coherence and full integration of the activities of DMSP within the relevant LIH units and within LCSB, thereby enabling the innovative transversal character of the platform. 

“By using stem cell-based models we can test a large library of different, already FDA (Food and Drug Administration) approved drugs, with the objective to repurpose existing compounds initially validated for specific conditions to treat patients with other medical indications. Aspirin, for example, was developed for headaches, but may also be used to prevent strokes”, says Prof. Krüger.

The cell models used in the laboratory help to understand and to modulate the molecular pathways. “When we observe that a protein is missing, for example, we screen for compounds that may bring the protein back. Or if we know that a new receptor plays a role in disease modulation, we investigate which drugs can selectively activate this receptor”, Prof. Krüger explains.

“The joint efforts between our research groups at LCSB and LIH and the ability and willingness of the staff of the two institutes to adopt a ‘one-team’ mindset have allowed us to set up DMSP as the first successful inter-institutional drug screening platform in Luxembourg. I am positive that our approach will continue to support the delivery of impactful results of valuable translational interest”, states Dr Yong-Jun Kwon, Head of DMSP.

“Our institutions have a common ambition: further developing Luxembourg into a renowned centre of excellence in research and innovation and to offer high-quality education to undergraduate and postgraduate students. For this, collaboration and pooling expertise are key”, says Prof. Jens Kreisel, Vice-Rector for Research of the University.

“The LIH-University of Luxembourg framework agreement builds on the deep trust and respect between the institutions, their leadership and researchers, which has been strengthened through Research Luxembourg, particularly during the pandemic”, says Prof. Ulf Nehrbass, CEO of LIH. “It is this coordination and alignment which will ensure international competitiveness for the years to come”, he concludes.  

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Luxembourg researchers receive prestigious international award

Dr Andy Chevigné and Dr Martyna Szpakowska from the Luxembourg Institute of Health (LIH) were awarded the prestigious 2019 Galien Prize for their outstanding contribution to molecular pharmacology.

Dr Andy Chevigné and Dr Martyna Szpakowska from the LIH Department of Infection and Immunity (DII) were rewarded for their outstanding contribution to molecular pharmacology during a virtual ceremony on Tuesday, December 8th, in the presence of Frank Vandenbroucke, Belgian Minister of Public Health and Social Affairs, and of representatives of pharmaceutical companies and healthcare hubs. The Galien Prize is traditionally organised in Belgium and Luxembourg by Roularta HealthCare on a yearly basis and crowns the most significant discoveries in the fields of pharmacology, drug development and medical devices.

Dr Martyna Szpakowska and Dr Andy Chevigné ©LIH

The two LIH researchers were commended during an online ceremony for their continuous achievements in advancing the understanding of the relevance, role, function and pharmacology of atypical chemokine receptors (ACKRs) and their ligands. ACKRs are “molecular switches” that interact with small molecules known as chemokines, thereby regulating cellular mechanisms such as cell growth and survival and consequently influencing a variety of physiological and pathological processes, including immune responses and immunosurveillance. Due to their involvement in several inflammatory and autoimmune diseases, as well as in many cancers, ACKRs have recently emerged as highly promising potential drug targets, although their biology is currently insufficiently understood.

The 2019 Galien Prize in Pharmacology is a recognition of Dr Chevigné’s and Dr Szpakowska’s efforts over the last eight years to extend their research activities and establish the first molecular pharmacology academic laboratory in Luxembourg. The research laboratory of “Immuno-Pharmacology and Interactomics” is located at the LIH Department of Infection and Immunity and co-supervised by the two laureates. The main objectives of their research group are to investigate the roles of chemokines and their receptors in immune disorders, cancer, viral infections and neuro-inflammatory diseases, ultimately leading to the development of drugs targeting these molecular components.

As part of the award ceremony, Dr Chevigné presented his team’s work to the expert audience through the presentation “Understanding the molecular pharmacology of human atypical chemokine receptors”.

“We are humbled and grateful to the jury for this unique opportunity. The Galien Prize is the highest accolade for pharmaceutical research and development and competition was indeed very strong. I am therefore extremely proud of the work we have been able to accomplish so far. This achievement will give additional visibility and credibility to the research performed at LIH and in Luxembourg in general” states Dr Chevigné, Principal Investigator and Group Leader of the Immuno-Pharmacology and Interactomics group.

Receiving the prize has been even more gratifying considering that it has been awarded to Luxembourgish researchers for the first time in 38 years! This is a further confirmation of the excellent international reputation of our institute and of the Grand Duchy as a whole”, adds Dr Martyna Szpakowska.

Our goal is to perform research that can be translated into concrete applications with tangible benefits for patients. The award of the Prix Galien to our scientists is a confirmation of the success of our efforts in this direction”, states Prof Markus Ollert, Director of the LIH Department of Infection and Immunity. “I also take the opportunity to extend my heartfelt gratitude to the organisers of this initiative, as well as to the Luxembourg National Research Fund, the Ministry of Higher Education and Research and the charitable initiative ‘Télévie’ for the generous and unwavering support”, he concludes.

Organised yearly by Roularta HealthCare, editor of the “Journal du Médecin/Artsenkrant”, the Galien Prize in Pharmacology consists of a gold medal and a sum of EUR 5,000. It is granted to a scientist or group of scientists under the age of 40 performing clinical or fundamental pharmacology research within a Belgian or Luxembourgish academic institute.

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When the drugs don’t work

Chemical compounds can have several stable forms – with dramatic consequences. A physicist at the University of Luxembourg can predict when this can occur: he has develop methods to precisely calculate the stability of molecules. These tools are now used by hundreds of scientists worldwide. They could also help understand why the new coronavirus is so contagious.

This article was originally published by the Luxembourg National Research Fund

It happened again. In 2008, the Parkinson drug Neupro had to be recalled from pharmacies, because it appeared that some of the pills were less soluble than the original and could not be properly absorbed by the body. A similar case had happened a decade earlier with the HIV drug Norvir.

Prof Alexandre Tkatchenko | ©️ FNR / Rick Tonizzo

The problem lies in the solid formulation of the drugs, explains Alexandre Tkatchenko from the University of Luxembourg. It should ensure that they can be correctly absorbed by the body and released. But sometimes, the crystalline structure has several stable forms with different properties. A very slight change in the production facility can then create batches of drugs which are not soluble and therefore cannot be absorbed by the body.

“Not only do we need to know which microbes are involved but above all what they really do,” explains the biologist. “The interplay between certain bacteria and a disorder will happen via molecules which can trigger a cascade of reactions in the body, for example, by interfering with biochemical pathways. What we aim to do is to “Chemists can monitor production if they are aware that the drug has several stable forms,” says Tkatchenko. “But sometimes they don’t know it is possible. This is where my work can be very useful, by alerting them of the possibility.”

Wave matters

The Russian-born physicist studies the behaviour of large molecules with unprecedented detail. Crucially, he takes into account the effects of quantum physics, the theory which describes the microscopic world in terms of overlapping waves.

“Many models until now neglected quantum effects or used simplifications too crude to be accurate. Our work has shown that they are actually crucial in many cases and were behind the problem of the Parkinson drug Neupro.”

His team has been developing computer simulations of molecules for a decade now, improving them bit by bit. These algorithms are published and reused by hundreds of physicists, biologists and chemists worldwide, including many working in pharmaceutical companies.

“Our methods have been used to analyse at least 50 different drugs, but I don’t always know who uses them: sometimes they cite us, sometimes not. But the important thing for me is that my work is useful to others.”

Quantum life

The same techniques are useful to study proteins, large molecules made of thousands of atoms and involved in numerous mechanisms in living organisms. The Luxembourg team recently discovered that quantum effects play an essential role in the way proteins fold, a fundamental process where they acquire the shape that enables them to function.

“Proteins often work by locking into other macromolecules, like a key fits only a specific lock. Our calculations have shown that quantum effects related to the wave characters of electrons make the unfolded protein more stable when it is diluted in water, which is always the case in living organisms. This shows that quantum physics, which has been used in inanimate devices like lasers or microchips, has an impact on life itself.”

Tkatchenko’s models could help explaining the virulence of some pathogens, such as the novel coronavirus.

“It is known to attach to ACE2, a protein situated at the surface of human cells which are in particular found in lungs. Other coronaviruses bind to the same receptor, but SARS-Cov-2 does it much more strongly, which probably contributes to its high contagiousness. To understand this strong binding, we want to look in detail at the way the viral protein, which has the shape of a spike, locks into ACE2. I expect that quantum effects play an important role.”

Machine learning meets quantum mechanics

The key for the reliable analysis of complex molecules is to find models which are precise enough without taking too much computing resources. 

“We have now developed a very robust model to describe the way distant parts of molecules influence each other. But an additional part deals with forces at short range. As it actually depends on the configuration of the first part it should be solved again and again at each step of the calculation, which requires a lot of computation time.”

To overcome this problem, the physicist’s team turned to machine learning, the technique that allows algorithms to learn to recognize images or to beat humans at chess. They fed an algorithm with a training set of data linking a certain configuration of the first, long-range part to an adequate model for the second, short-range part. It can then learn to guess very rapidly what model should be used at each step of the calculation, which makes the simulation fast enough to be practical.

“Simulating a large molecule is always a balancing act,” says Alexandre Tkatchenko. “If you include too many details, the calculations take weeks. If you oversimplify the model, you get results which are not reliable. It’s a question of finding the right balance. This is what I like in this work.”

About the European Research Council (ERC) 

The European Research Council, set up by the EU in 2007, is the premiere European funding organisation for excellent frontier research. Every year, it selects and funds the very best, creative researchers of any nationality and age, to run projects based in Europe. The ERC offers four core grant schemes: Starting, Consolidator, Advanced and Synergy Grants. With its additional Proof of Concept grant scheme, the ERC helps grantees to bridge the gap between grantees’ pioneering research and early phases of its commercialisation.

Latest news Personalised Healthcare

What microbes really do in our guts

Countless microorganisms live peacefully in our body, but they also can be involved in many diseases. To find out exactly what role they play, a biologist has given himself a Herculean task: survey all the biomolecules produced by the microbes residing in our guts.

This article was originally published by the Luxembourg National Research Fund

You, as a body, are never truly alone. Each of us harbours an incredibly large number of bacteria, viruses and fungi: around tens of billion in total, slightly more that the number of human cells.

Most of the time, these strangers live with us in good harmony. But changes in our microbes’ population, our so-called microbiome, have been found to be related to many diseases – via mechanisms that remain largely unknown. To understand what exactly happens in our stomach and intestines, Paul Wilmes from the University of Luxembourg has a grand plan: survey all the molecules produced by the microbes living in our body and unravel their relationships to diseases.

Prof Dr Paul Wilmes © FNR / Rick Tonizzo

“Not only do we need to know which microbes are involved but above all what they really do,” explains the biologist. “The interplay between certain bacteria and a disorder will happen via molecules which can trigger a cascade of reactions in the body, for example, by interfering with biochemical pathways. What we aim to do is to find out which microbes are involved in a disease, list and analyse all the molecules they produce to understand how these affect our health. If we succeed, our work could allow many new therapeutic approaches for chronic conditions which currently have only a few treatments or none at all.”

The researcher’s team in Luxembourg is focussing on three diseases: Parkinson’s, rheumatoid arthritis and type-1 diabetes. These conditions are all related to chronic inflammation, which is known to be associated with changes in the human gut microbiome. 

For the first part, Paul Wilmes’ team has developed impressive tools to process samples and make them ready for biochemical analyses automatically.

“Because stool is very heterogeneous, it is crucial to use for the analysis a representative sample and extract as much information from this sample as possible,” explains the researcher.

His team has built a robotic platform that takes a small sample and cracks microbes open to extract the biomolecules contained within, separate them from the products found outside, and sort all the compounds according to their chemical properties. These include DNA and RNA, peptides, proteins, lipids and carbohydrates. In the last step, the molecules are analysed by various techniques: genetic sequencing as well as gas and liquid chromatography coupled to mass spectrometry.

Why Parkinson’s starts in the guts

The researchers have already some preliminary results for Parkinson’s disease. After having observed different microbial populations in healthy and sick persons in 2017, they were recently able to identify one specific molecule that could help understand the role played by microbes in the disease.

“It seems surprising that a neurological condition like Parkinson’s might originate in the gut, but this is a long-standing hypothesis,” says Paul Wilmes. “It is for example possible that a microbiome-derived molecule may be involved in the pathogenesis of Parkinson’s in the gut. It might take decades for the disease to spread from the gut to the brain and it might be only at a rather advanced stage that the disease then really manifests itself through the classical Parkinsonian symptoms.”

On an empty stomach

To go one step further, the team has partnered with German hospitals in Berlin and Kassel. They will observe the changes in the biomolecules found in the gut while patients follow a fasting regimen aimed at lessening the symptoms of either Parkinson’s or rheumatoid arthritis.

“By tracking the changes over time, we hope to be able to show causality: that the presence of certain molecules is really the cause of a disease and not a mere consequence of it.”

The project will recruit 30 patients for each of the two diseases who will undergo therapeutic fasting for one year. First, their guts are emptied with the help of laxatives in order to get rid of most of the gut microbes and their biomolecules. The patients reduce their food intake for a week to a modest 400 kilocalories per day (a sixth of the usual recommendations) in the clinic, which deprives the bacteria in the gut of their nutrients and lessens their activity.

This allows the scientists to precisely follow the evolution of the concentration of biomolecules by analysing stool samples, and to compare them with the reappearance of the disease’s symptoms and evolution of specific biomarkers in the body. After the intervention, the patients are followed for a year during which time they follow a dietary maintenance regimen.

A gut in a shoebox

The last step is to precisely study the effect of the specific microbes and molecules uncovered in the first parts of the project. For this, Paul Wilmes and his colleagues use a device the size of a shoebox which they had developed previously to simulate the gut. A series of small chambers connected by microfluidic channels replicate the different parts of the digestive tract, such as the small and large intestines, which have different environmental conditions and microbe populations. The scientists can then analyse what happens when human cells, grown in the presence of oxygen, interact with specific microbes, cultivated without it.

“This tool could be used to check whether a drug can inhibit the production of a pathogenic microbial molecule product,” says the biologist. “This could be very useful in drug discovery and testing. We are currently planning to launch a start-up to offer such services to pharma companies.”

About the European Research Council (ERC) 

The European Research Council, set up by the EU in 2007, is the premiere European funding organisation for excellent frontier research. Every year, it selects and funds the very best, creative researchers of any nationality and age, to run projects based in Europe. The ERC offers four core grant schemes: Starting, Consolidator, Advanced and Synergy Grants. With its additional Proof of Concept grant scheme, the ERC helps grantees to bridge the gap between grantees’ pioneering research and early phases of its commercialisation.