FNR PEARL Chairs: Prof Rejko Krüger – connecting fundamental research and clinical care

my name is like ah-oogah I'm a neurologist by training and I'm doing neuroscience research but also clinical research and I'm seeing patients at the Santos Battaglia here in Luxembourg neural degeneration is essentially premature aging of cells so all our body ages over time but there's a certain group of specific cells that each faster than the whole organism if these are cells in the brain involved in movements involuntary movements then you could get Parkinson's disease and this is what we see in our patients in 2014 professor Michael Kruger came to Luxembourg in the scope of the Perl program of the Luxembourg national research fund his mission was to build a bridge between clinical patient care and basic research and ultimately improve our understanding of Parkinson's disease one of the core projects of his team is to establish a large nationwide Parkinson's patient cohort of 1,600 patients and healthy people living in Luxembourg and the greater region blood samples are used to identify biomarkers in patients that allow a better understanding of the causes and progression of Parkinson's disease neuropsychological tests can provide further insights into certain symptoms of the disease that may be less known for example at loss of smell but which often provide very early indications of the disease Parkinson's also restricts coordination and mobility testing these restrictions provides valuable information as to the extent of disability most affected are complex sequences of movements involving both hands we have an even our funded projects a national center for excellence and research which allows us to invite patients to actively contribute to that research and many patients are highly motivated to support our research sometimes they say this is not for me even if I can help the next generation I'm happy to do that but I think that can already profit now at the Luxembourg Center for systems biomedicine Reiko Kruger and colleagues are also breaking new ground in the research of innovative treatment approaches the first step is to distinguish between different types of Parkinson's rare genetic forms and the more common so called sporadic form of the disease which may be initiated by impaired clearance of certain proteins from the cell that cause a certain type of neuron in the brain to age faster and lose function another entirely novel approach of the research group is to take skin cells donated by Parkinson's patients and revert them to a kind of embryonic like state using chemicals this yields so-called pluripotent stem cells the experts can induce these cells in the lab to transform into brain cells of the type that is affected in Parkinson's patients with the help of a fully automated and worldwide unique screening system the researchers then use these neurons derived from the patients to test which substances could be potentially suitable for treating Parkinson's this has already yielded its first successes in the laboratory they have already managed to restore the functionality of cells from a patient with a very rare hereditary form of Parkinson's our study is really proof of concept it would be the first personalized treatment approach for Parkinson's disease by understanding the underlying mechanism and by specifically intervening into that mechanism to bring back cellular function and this is the concept of truck repurposing that means that we use compounds that have been already applied in other diseases until new drugs are officially available the priority is to employ new techniques to diagnose the disease at earlier stages to understand it better and to slow down disease progression to hold off the more severe symptoms the researchers latest project is to integrate smart shoes these have sensors in the soles for analyzing the patient's walking gait this can show us specific symptoms like trembling in place at a very early stage and it shows us alterations for instance reduction of step length which can be also an early sign of developing Parkinson's disease on the other hand it can be even used in patients with definite Parkinson's disease to control the treatment because I can get information that I could not get from my clinical examination potentially even in the home environment in real life because the sensor gives information back to me and shows oh there was a problem there was a fall there was a trampling situation and then I can adapt therapy the measurements from the shoes are prepared in cooperation with data analysis experts at LCS B and the University of Erlangen the ultimate goal is to identify different variants and stages of the disease from patterns in the gait of afflicted people this is a big data application that requires enormous computing capacity and which has only been conducted in Luxembourg so far from my point of view is a Perl really provided a critical step towards next-generation medicine for me it was really a boost to get into what we imagine as an integration of clinical research and fundamental research and I think it is in the context of what has been already established in Luxembourg at the Luxembourg Centre for systems biomedicine but also with the partners from the Luxembourg Institute of Health from the integrated biobank Luxembourg and from the Santo hospitality looks anbu where we have all the opportunities to bring together these resources that really translates into what I always like to call medicine 2.0 where we have more adapted more stratified therapies and an earlier diagnosis of neurodegeneration

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