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

My name is Rejko Krüger and I’m a neurologist by training I do neuroscience research, but also clinical research, and I see patients here at the Centre Hospitalier in Luxembourg Neurodegeneration is essentially the premature ageing of cells Our body ages over time, but there is a certain group of specific cells that age faster than the whole organism If these cells are in the brain, involved in movements – involuntary movements – then you can get Parkinson’s Disease This is what we see in our patients In 2014, Professor Rejko Krüger came to Luxembourg in the scope of the PEARL programme of the Luxembourg National Research Fund (FNR) His mission was to build a bridge between clinical patient care and basic research and ultimately to improve our understanding of Parkinson’s Disease One of the core projects of Rejko and his team is to establish a large nationwide Parkinson’s patient cohort of 1600 patients and healthy people living in Luxembourg and the greater region Blood samples are used to identify biomarkers in patients that allow for 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 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 FNR-funded project, the National Centre for Excellence in Parkinson’s Research (NCER-PD), which allows us to invite patients to actively contribute to this research Many patients are highly motivated to support our research Sometimes they say ‘this is not for me, but if I can help the next generation, I am happy to do it’, but I think they can already benefit now At the Luxembourg Centre for Systems Biomedicine (LCSB), Rejko Krüger 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 sporadic form of the disease, which may be initiated by the impaired clearance of proteins from the cell that cause a certain type of neuron in the brain to age faster and lose function Another entirely novel approach by the research group is to take skin cells donated by Parkinson’s patients and revert them to an 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 are affected in patients with Parkinson’s 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 personalised treatment approach for Parkinson’s Disease By understanding the underlying mechanism and by specifically intervening into that mechanism to bring back cellular function This is the concept of drug repurposing: we use compounds that have already been 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 analysing the patient’s walking gait This can show us specific symptoms, such as trembling, at the very early stage It also shows us alterations, for example reduction of step length, which can also be an early sign of developing Parkinson’s Disease On the other hand, it can be used to control the treatment of patients with confirmed Parkinson’s Disease, 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 sends information back to me and shows me if there has been a fall or a trembling situation, and then I can adapt the therapy The measurements from the shoes are prepared in cooperation with data analysis experts at LCSB 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, the PEARL 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, in the context of what has already been established in Luxembourg at the LCSB, but also with the partners from the Luxembourg Institute of Health, the Integrated Biobank of Luxembourg, and from the Centre Hospitalier de Luxembourg. Here we have all the opportunities to bring together these resources that really translate into what I like to call ‘Medicine 2.0’, where we have more adapted therapies and an earlier diagnosis of neurodegeneration.

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