Prevent activation of the cellular receptor, which slows growth and causes achondroplasia. A groundbreaking method of treating genetic disorders of growth has been described by scientists from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) and Masaryk University in Brno, together with Japanese colleagues.

The key substance in this case is an RNA aptamer with the James Bond name RBM-007, which acts as a ligand trap. Ligands are usually small proteins that form complexes with cellular receptors and can activate them. In the case of achondroplasia, it is the FGFR3 receptor whose increased activity slows the growth of cartilage cells. An aptamer is an engineered portion of a ribonucleic or deoxyribonucleic acid that binds to a ligand that can no longer activate FGFR 3 receptors, thereby preventing growth disorders.

Pavel Krejčí, head of the FNUSA-ICRC Cell Signaling research team, contributed significantly to this discovery. “The Japanese company developed this RBM-007 for the treatment of AMD (Age-related Macular Degeneration), however, we noticed its potential for the treatment of growth disorders and started working in this area,” Krejčí described the beginnings of the cooperation. That was five years ago and now RBM-007 is entering the first phase of clinical trials and is being tested in Japanese patients. The results are very promising, however, testing a new drug is a long way off. “Drug for achondroplasia – Vosoritide, which I participated in the research, will reach the first patients after more than sixteen years,” Krejčí added.

The main focus of the FNUSA-ICRC Cell Signaling team, ie research into receptor tyrosine kinases, which currently includes FGFR3, is far from over. “Currently, we have about fifteen projects under development,” Krejčí confirmed. One is the study of aptamers that would not function as a ligand trap but inhibit receptors directly. The result could be a new generation of molecules with great potential for the treatment of diseases related to damage to various organs, not just bones. “We are trying to create a bridge between basic and clinical research. So far, we are doing well, hopefully it will last in the future, ” added Pavel Krejčí.

The publication was published in the prestigious journal Science Translational Medicine and can be found here:

Achondroplasia is a genetic form of dwarf growth, the height in adulthood in those affected by this disease is on average 125 cm. It is the most common form of genetic growth disorder in humans, and is caused by mutations in the FGFR3 gene. In the Czech Republic, 4-5 children with this disorder are born annually. Four years ago, scientists from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) founded register of these children, thanks to which they collect data on their health.

RNDr. Jan Fröhlich, Ph.D. and Dr. Manlio Vinciguerra of the Epigenetics, Metabolism and Aging FNUSA-ICRC Research team, in collaboration with a research institute at the Medical University in Varna, published a successful review summarizing current knowledge on the effect of adipomyokines / metabotrophic factors on the development and progression of cardiometabolic (CMD) and neurodegenerative diseases. The work was published in the International Journal of Molecular Sciences.

“Over the last 30 years, there has been a significant change in the view of adipose tissue, which is now understood as an important regulator of metabolism and one of the main endocrine organs of the human body,” says Dr. Jan Fröhlich with the fact that adiopobiology has thus become an important scientific field, dealing, among other things, with the study of the origin and consequences of obesity. It plays an important role in the pathophysiology of cardiometabolic and neurometabolic diseases, including Alzheimer’s disease (AD).

“According to the latest findings, one of the main risk factors for the onset and progression of Alzheimer’s disease is obesity and the associated hypertension, high LDL cholesterol and diabetes. On the contrary, numerous studies in mouse models and volunteers have shown that starvation-induced diets or short-term exercise have a beneficial effect and slow the development and progression of neurodegenerative diseases, including AD, ”explains Dr. Jan Fröhlich.

It has been shown that mediators of positive effects are factors / hormones secreted from skeletal muscle and adipose tissue, so-called adipomyokines. Adipomyokines are a heterogeneous group of metabolites and proteins that have a direct effect on metabolism and are therefore also nicknamed metabotrophic factors. “In our work, we point out that therapies based on the modulation of metabolism through the administration of metabotrophic factors could in the future help patients suffering from serious cardiometabolic and neurodegenerative diseases,” points out Dr. Jan Fröhlich.

The full article is available HERE.

The Hands-on Computational Enzyme Design Course is a highly practical and interactive course meant primarily for protein and metabolic engineers with no prior experience in computer modelling and bioinformatics. Other experts willing to broaden their current computational protein design toolbox can also benefit from this course. A team of experts and software developers provide training on how to operate several software tools devoted to different aspect of enzyme engineering, and how to properly interpret the results. Four main topics covered are: (i) Mining and analysis of novel enzymes, (ii) Engineering protein stability, (iii) Engineering enzyme activity and specificity, and (iv) Engineering protein solubility. The theoretical background and practical exercises are provided in a dynamic discussion environment.

The first edition of this course was carried out in the classical on-site format for 3.5 days, in Brno, Czech Republic, in February 2020. The course was organized by the Loschmidt Laboratories, Department of Experimental Biology and RECETOX, Faculty of Science, Masaryk University and International Clinical Research Center, St. Anne’s University Hospital Brno. Due to the COVID-19 pandemic, the second edition of the course was performed on-line in May 2021. Both editions were fully booked and the feedback from the participants was very positive. The great majority of the participants was highly satisfied and would recommend the course to a colleague. The 2nd edition was fully booked after only 2 weeks, with participants from 16 countries and 4 continents, 12% of them coming from industry. Our experience shows that: (i) by running an on-line edition we shortened distances, allowing participants from farther regions of the globe to join, (ii) the demand for training on computational enzyme design tools is high, and (iii) the reputation of the Loschmidt Laboratories as providers of valuable tools and training is growing.

We plan to run in the future both on-site and on-line versions of the course. If you are interested in participating in the next edition, you can access the course website and sign up to our newsletters to stay tuned!
Contact: Dr. Serqio Marques – smar96@gmail.com

Improving the quality of care for human resources, transparent recruitment and selection of employees, support for the development of professional growth, equal working and salary conditions for women and men and many other benefits. All this means the HR AWARD, which confirms that the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) guarantees excellence in caring for the working conditions of her researchers.
The award given by the European Commission is one of the most prestigious in the field of HR and is widely recognized in the international scientific community. “In the case of a foreign job applicant at our center, inquiries about the HR AWARD are very common,” confirmed Silvia Vašulková, HR Award Officer of FNUSA-ICRC. The share of foreign workers in our center is very high, out of the total number of 425 employees it is almost twenty-five percent.
However, the work on improving processes in the field of HR does not end there, on the contrary. “Now we have and want to fulfill all the projects and tasks contained in our action plan, in two years we will have an internal evaluation and its eventual revision,” added Silvia Vašulková. After its implementation, our center awaits evaluation directly by the European Commission.

All information about HR AWARD can be found here:

On Saturday, May 15, we commemorate the Day of the Fight against Stroke. St. Anne’s University Hospital Brno, together with the Sarema Rehabilitation Center, prepared a live broadcast on the topic on her Facebook page. Stroke is the second most common cause of death in the world. Every fourth person is at risk and affects patients regardless of age. There are no exceptional cases where the stroke affected the mother during childbirth, the patient with COVID-19 or the driver while driving. It is important to get to the hospital as soon as possible and start intensive rehabilitation as soon as possible after treatment.

Head of the Stroke research team of the The International Clinical Research Center of St. Anne’s University Hospital Brno and professor of neurology Robert Mikulík emphasizes that patients should not be transported to the hospital on their own axis. “If the patient travels on his own, he may arrive at the hospital without a stroke center, which provides comprehensive care for patients with cerebrovascular problems. On the contrary, when he dials 155, the rescuers themselves will contact a suitable doctor or medical facility, ”says prof. MUDr. Robert Mikulík, Ph.D., who, in addition to the research center, also works at the 1st Department of Neurology, FNUSA and LF MU.

If stroke treatment is to be effective, it must be started as soon as possible, ideally within 4.5 hours of the onset of symptoms. Time is crucial for a stroke. The sooner the patient enters the hospital, the higher his chances of recovery. Professor Mikulík also draws attention to an interesting phenomenon, namely the direct connection between COVID-19 and the occurrence of stroke. “Although it has already been shown that COVID-19 can cause stroke and the number of patients should increase, we paradoxically recorded about 15% fewer cases in the hospital during the spring of 2020,” he points out that people should not risk serious consequences and during a pandemic seek professional help.

Equally important is the early start of intensive rehabilitation, as explained by Mgr. Tereza Valíková from the Sarema Rehabilitation Center: “The sooner we start, the sooner we will address the brain and neuroplastic processes. When we start later, we often encounter patients who have already developed poor compensatory habits, which are more difficult to break down, ”he says. Thanks to the start of intensive rehabilitation in time, Mrs. Eliška, who suffered a hemorrhagic stroke during childbirth, is also slowly returning to life. “Eliška had a tumor in her head that was not known. Apparently, due to the pressure at birth, there was bleeding from the tumor and a large swelling of the brain. She fell into a coma at night. After midnight, she was taken by ambulance to the hospital and operated there urgently. The tumor was successfully removed, but the swelling of the brain managed to do great damage, “recalls Eliška’s husband, Petr. His wife is now training intensively at the Sarema Rehabilitation Center and is making great progress, which you can follow on the website www.proelisku.cz. However, due to long-term stays in therapies, she cannot see her two sons as often as she would like.
“Complete cure depends on several factors, such as the extent, age and timeliness of care. Therefore, if you suspect a stroke, contact emergency services immediately. The consequences do not have to be any or minimal, ”adds Tereza Valíková.

For more information, on Saturday 15 May at 5 pm, those interested can “tune in” to a webinar called The Story of a Stroke: The Patient’s Journey. They will learn what the first minutes of a patient look like after arriving at the hospital and how to properly rehabilitate the brain. Just join the event at this link , or the Facebook page of FNUSA-ICRC or FNUSA, who will share the broadcast.

An important research team within the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) is Kardiovize. It is a cardiovascular prevention program in Central and Eastern Europe based on population analysis. One percent of the population of the city of Brno participates in it and the data from the research have a large international overlap. Its importance is also confirmed by the head of the research team, Dr. Juan Pablo Gonzalez Rivas: “Cardiometabolic risk factors, including obesity, diabetes, hypertension and dyslipidemia, are the leading cause of death and disability worldwide.”

However, this burden affects populations disproportionally, „It is very important to understand how to stop the consequences of cardiometabolic risk factors globally, and the heterogeneity of the drivers that creates the disease varies considerably across regions, cultures, and ethnic groups, for this reason, it is mandatory to approach the understanding of this problem using a multicultural perspective“, says Dr. Gonzalez Rivas.

This fact was also the reason for the creation of the international consortium METRICS, which was established last year. Kardiovize is a founding member of the consortium and Dr. Gonzalez Rivas is its secretary. METRICS is the result of a long-term collaboration with a group of scientists from Venezuela, led by Ramfis Nieto-Martinez and Dr. Jeffrey I. Mechanick of Mount Sinai, NY, USA. “We have published sixteen articles with this group in the last seven years,” said Dr. Gonzalez Rivas. “We meet regularly every month and continue to actively cooperate on our projects.”

Currently, the consortium has 29 members from four continents, such as Masaryk University in Brno, Universidade Federal Fluminese in Rio de Janeiro, Charles University in Prague, Harvard School of Public Health in Boston and the Mayo Clinic. These are not only medical and PhD students, but also top scientists. “We are very proud of our diversity and I would like to emphasize that this is not a closed society, anyone can join us and will be welcome,” added Dr. Gonzalez Rivas. Five members of Kardiovize itself are involved, each of whom presented at least one project related to public health issues last year, and another five projects are currently being prepared.

We asked Dr. Gonzalez Rivas – can a medical student from Masaryk University in Brno, for example, get involved in the activities of the consortium?
Of course, one of the core values we have in our research team is to support junior researchers and interns. For example, Anna Zimovjanová, one of our interns, approached us with the idea of a project aimed at evaluating the impact of social determinants on the mental health of medical students. Both mental health and the social situation are among the risk factors associated with cardiovascular disease. So we in Kardiovize helped her with the preparation of the project and she also introduced it to the members of METRICS. They provided it with feedback and in June she will present a supplemented proposal for the implementation of this project and its implementation in seven countries, which we consider a huge success. This is exactly the goal of the cooperation between the Kardiovize team and the METRICS consortium, ie to offer a platform for the development of our own projects. I would just like to add that Anna Zimovjanová is also a recent research assistant in our team while studying at Masaryk University.

More information about the METRICS consortium can be found on the website. Alternatively, you can contact Dr. Gonzalez Rivas (juan.gonzalez@fnusa.cz).

Kardiovize research team of the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) has published a new publication dealing with visceral fat. This is the first such published study in Europe.

The new Kardiovize publication deals with visceral fat, ie fat stores that are stored around vital organs. “It turned out that we can’t use the values of visceral fat defined by colleagues in the USA or Japan to determine cardiovascular risk. The local population has very different values, “said the head of the FNUSA-ICRC Kardiovize research team, dr. Juan Pablo Gonzalez Rivas. The publication was published in the professional journal Obesity Research & Clinical Practice.

A young researcher, Anna Polcrová, who studied Nutritional Therapy at the Faculty of Medicine of Masaryk University, Social Epidemiology at the Faculty of Science of Charles University and continued her studies at Masaryk University while working in the Kardiovize team. “Body fat can be stored in the human body in various areas. In principle, we distinguish between subcutaneous fat, which is located under the skin, and visceral fat, which is located inside the abdominal cavity and surrounds our organs. It is the placement of fat stores in the body that significantly affects its impact on our health. Previous research has found that fat placed under the skin is not as risky as visceral fat, because excess visceral fat is associated with metabolic abnormalities such as insulin resistance, diabetes II. type, increased risk of thrombosis or endothelial dysfunction, ie disorders of the inner lining of blood vessels. ”

And how is the level of visceral fat in the human body actually measured? A generally accepted standard method is computed tomography, which is, however, relatively expensive and exposes the patient to radioactive radiation. “We used bioelectrical impedance analysis in the patients in the study, which has the advantage of simplicity, speed and also lower costs. It is non-invasive and shows a strong correlation with the values measured by computed tomography. The bioimpedance method is based on weak electricity flowing through the body and measurements to calculate impedance (resistance), which allows to describe the composition of the human body, including areas of visceral fat. Although it may sound dangerous, this method is completely painless and can be used for people of any age. The only contraindication is the presence of a pacemaker or pregnancy, “added Anna Polcrová.

To create this analysis, the researchers used the data of 2052 participants in the long-term study Kardiovize, which is ongoing at FNUSA-ICRC. Since 2013, it has been monitoring the health of a sample of the Brno population aged 25-65, and the second wave of examinations will be completed this year. “Our results showed that the limit values of visceral fat related to cardiometabolic risk in the Czech population are different in comparison with previous studies in other populations. We observed that 90 cm2 limits in men and 109 cm2 in women were associated with the presence of cardiometabolic risk factors including high waist circumference, increased blood pressure, decreased HDL-cholesterol (so-called “good” cholesterol), elevated triglycerides and elevated glucose levels on an empty stomach. In addition, men had a higher risk of cardiometabolic complications with lower visceral fat levels compared to women. Briefly, the results showed that the distinction between high and low visceral fat and associated cardiometabolic risk must be based on population-specific cut-off values, while taking into account gender differences. The amount of adipose tissue in the body, which is assessed as the norm for women, can be considered risky for men. And it works the same way among members of different ethnicities, “added Anna Polcrová.

It should be added that a new study by the Kardiovize research team was also selected for publication in the form of an e-poster at the prestigious European Congress on Obesity. A total of 330 e-posters were received (three from FNUSA-ICRC), but only 20 of them were selected for oral presentation, two of them from FNUSA-ICRC. Among them is also the work of Anna Polcrová.

Anna_Polcrova

On 25th May 2021, Alliance4Life organizes the kick-off meeting of its new Horizon 2020 project titled Alliance for Life Sciences: From Strategies to Actions in Central and Eastern Europe (A4L_ACTIONS).

It is a continuation of the successful Alliance4Life project, which was initiated by the CEITEC Masaryk University institute with a clear mission to help bridge the innovation gap between Western and Eastern Europe. The ten founding members, including our center, formed the alliance as a permanent structure in Vilnius in October 2019 with the signing of a Memorandum of Understanding and continued to work together in a difficult year 2020. Two new member institutions from Bulgaria and Romania were invited to the A4L_ACTIONS project.

A4L ACTIONS aims to increase the attractiveness of science centers in Central and Eastern Europe for cooperation with Western Europe, which will have an impact on Europe-wide research excellence and the impact of scientific research on society, human health and quality of life. A4L ACTIONS builds on the results achieved under A4L and will seek to further develop them in the following areas:
– Culture fostering excellence: piloting peer-evaluation and assessment of institutional practice as a strategic management tool, professionalizing research administration;
– Recognition and trust towards CEE: attracting advanced partners to identified pockets of excellence, supporting scientific ideas originating in CEE, initiating new international projects and collaborations with industry;
– Career policy nurturing talent: training and networking next generation of leaders, upgrading institutional career systems;
– Impact on innovation: raising the competences of Technology Transfer specialists, creating industry relations platform linking academia and industry;
– Spill-over effects: sharing, inspiring, communicating with stakeholders and policy makers; using the established networks to gain advice, new collaborations and EU-wide impact.

The plenary session will be open to all, registration is possible here:

A4L_Leaflet1    A4L_Leaflet2

From 2016 to 2020 the International Clinical Research Center at St. Anne’s University Hospital Brno (FNUSA-ICRC) was financed mainly from the National Sustainability Program (the NPU II project). At the end of this period, a final evaluation took place, where members of the opponent board from the Ministry of Education, Youth and Sports together with opponents from numerous other prestigious foreign institutions evaluated the project as excellent and with an international impact. FNUSA-ICRC´s scientists thus met the goals set by the contract and achieved excellent, internationally recognized results.

Within five years, FNUSA-ICRC has received subsidies from the NPU II project with the total amount of CZK 985 million. The final report states that the Center has made significant progress towards being an internationally competitive and sustainable, multidisciplinary center of excellence in translational medicine. Both in clinical and basic research.

The final report emphasizes, inter alia, that in 2020, FNUSA-ICRC continued to develop despite the unusual and unpredictable situation associated with COVID-19. “It should be noted that we had to restrict access to laboratories, and many scientists, nurses as well as administrators devoted their time to helping patients, working in test centers or supporting other hospital services,” said Pavel Iványi, MBA, LL.M., CEO of the Center. “That is why I think we´re talking about an extraordinary result and I thank everyone who made a contribution.”

In addition to all commitments being fulfilled and results achieved, the Board of Opponents also highlighted FNUSA-ICRC´s support of mobility (supporting students and enabling them to acquire new abilities, knowledge and skills) – 943 students from all over the world took part in the project and positively acknowledged the cooperation, for example in the form of joint grants. The number of implemented clinical trials is also exceptional, mainly because FNUSA-ICRC is the only so-called Prime Site in the Czech Republic for the global IQVIA group. Just to give an idea – there are currently 170 clinical trials in progress.

Many scientific outputs of FNUSA-ICRC have been published in leading international journals and are considered key in their respective scientific fields. For example, several articles appeared in the Top 10 ranking scientific journals, an average of 17% of the total number of FNUSA-ICRC´s publications to be exact and an average of 8% appeared in the Top 5. FNUSA-ICRC researchers have published their articles in Nature, New England Journal of Medicine, Lancet Neurology, Nature Reviews Neurology, etc.

The evaluation report also contains several recommendations for the future. In particular, greater deepening of cooperation in the international field, with domestic universities, and a continued involvement of students in scientific projects. “We are aware of all these challenges and we are working on them. For example, we are negotiating with Masaryk University to deepen our cooperation,“ said director Iványi. “We are also trying to fine-tune the funding system with our founder, the Ministry of Health, so that we can ensure certainty of function for already established international scientific teams and the Center itself.”

The main goal of the NPU II project was to enable FNUSA-ICRC to develop its existing scientific potential in basic, translational and clinical research. Especially focusing on fields of cardiovascular, neuroscience and oncological research, medical biology, biomedical engineering, molecular biology and stem cells. A clear advantage is the connection to St. Anne’s University Hospital Brno, which provides direct access to a large demographic of patients. This creates optimal conditions for translational medical research, focusing on various diseases (including cardiac arrhythmias, heart failure, sleep disorders, stroke, dementia and cancer).

FNUSA-ICRC_Building    FNUSA-ICRC_Research

Feeling lonely, worried about the health of their loved ones and stress from an unstable situation. The pandemic of the COVID-19 disease affected not only the physical health of the population, but also the mental health, which has now been confirmed by research in which researchers from the International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) and the American Mayo Clinic.

The researchers analyzed the impact of the pandemic and related restrictive measures on mental health in the participants of the Kardiovize project, a study that has been examining the local level of health for a long time on a population sample of one percent of the city of Brno. 715 Brno residents took part in the analysis of changes in mental health during the first hard lockdown in the spring of 2020, when, in addition to services, the borders of the Czech Republic were closed. “The results showed that the incidence of increased stress and depressive symptoms increased 1.4 to 5.5times compared to the period before the COVID-19 pandemic,” said PhDr. Jan Sebastian Novotný, Ph.D., first author of an international study and member of the Translational Neuroscience and Aging Program Research group FNUSA-ICRC. “This deterioration manifested itself in all age groups and was more pronounced in women,” he added.

The study also showed that, despite a comparable deterioration in all age groups during the pandemic, younger grades suffered more mentally, which may be due to work or study insecurity, and thus financial instability. At the same time, richer life experiences and lower expectations can be expected for older age groups, which also contributes to higher mental resilience in general. The main risk factors for deteriorating mental health have been feelings of loneliness, perceptions of COVID-19 as threatening, and some negative effects on lifestyle – such as the financial effects of restrictive measures, lack of exercise or deterioration in sleep quality. On the contrary, a higher level of resilience, ie the ability to maintain a standard level of functioning despite adverse circumstances, proved to be a protective factor.

“The observed increase in the incidence of stress and depressive symptoms as well as many identified risk factors can be prevented, diagnosed and treated. It is therefore necessary to respond to these findings in a timely and targeted manner by setting up appropriate psychological and psychiatric help so as to reduce the risk of a subsequent pandemic of mental disorders in the population, “said Jan Sebastian Novotný.

The FNUSA-ICRC research team continues the study, its goal is to capture the long-term effects on the mental health of Brno residents.

Novotny