Parkinson’s disease – from molecular mechanisms to patient care

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Frank Jons

Parkinson’s disease is the second most common neurodegenerative disease. It leads to symptoms like trembling, stiffness and general slowness of movements. Over time, a person with Parkinson’s may have trouble talking, swallowing or sleeping. It affects around 1000 people in Luxembourg, and 7 to 10 million worldwide. In all likelihood, these numbers will double until 2050. Both genetic as well as environmental factors are thought to play a pivotal role in the faster ageing and degeneration of dopamine-producing nerve cells that underlie this disease. But how exactly they trigger the pathological process in those cells is not clearly understood yet.

At the LCSB, Parkinson’s disease is at the core of our research. Using the combined expertise of the centre, we look at it from all angles to understand the molecular mechanisms behind this disease: Can we define subgroups of patients based on molecular and clinical characteristics? What is the role of mitochondria, the powerhouses of the cells, in Parkinson’s disease? Can we find new biomarkers in blood or urine with which we could diagnose the disease earlier, before motor symptoms occur? Can personalised 3D nerve cell cultures derived from patients’ skins cells help to find new therapeutics? How can we improve existing care options for people with Parkinson’s disease? Can we predict how the disease will evolve over time for each patient? What is the role of the gut microbiome or of environmental factors in the development of the disease?

Luxembourg Parkinson’s Study

In 2015, the Luxembourg National Research Fund (FNR) established the National Centre for Excellence in Research on Parkinson’s disease, in which five research institutes in Luxembourg combine their expertise on Parkinson’s disease. The LCSB plays a key role in this collaborative research program, led by Prof. Rejko Krüger. More than 1400 volunteers with and without Parkinson’s have participated already in the Luxembourg Parkinson’s Study to find new ways to earlier diagnose and better treat the disease. Combining clinical and psychological information, as well as molecular data from biological samples like blood or urine, LCSB researchers are looking for new biomarkers that differentiate patients from people without Parkinson’s disease. First results show promising differences in the molecular content of the blood and composition of the microbial community in the gut that will be further evaluated for clinical use as diagnostic marker. A brain bank has also recently been implemented, to facilitate studies based on brain tissue.

Improving Deep Brain Stimulation

One therapy option for the more advanced stages of Parkinson’s disease is Deep Brain Stimulation. Here, patients are surgically implanted with electrodes in specific areas of the brain. These can influence some of the symptoms, like tremor or muscle stiffness, through electrical activity. LCSB researcher around engineer Prof. Jorge Gonçalves and neurosurgeon Prof. Frank Hertel have developed computational approaches to more accurately position the electrodes and to adjust the electrical stimulation. In the future, they aim to develop combinations of novel electrodes and sensors that allow to detect the amount of dopamine released in the brain as well as evaluate the tremor the patient experiences. Using this kind of information in a feedback loop would allow to better tailor the stimulation to the specific needs of each patient at any given point in time.

Integrated, patient-centred care

In addition, we aim to improve the therapy patients already receive today. In 2017, the LCSB has established ParkinsonNet Luxembourg, based on an integrated care concept developed in the Netherlands. ParkinsonNet trains healthcare professionals, e.g. physiotherapist, speech therapist and ergotherapist, for the treatment of Parkinson’s patients, following on evidence-based international guidelines, and facilitates the information exchange between the different healthcare disciplines. This puts the needs of the patients at the center and simplifies their access to specialised care