On the 11th of April, patient organizations around the globe arrange the World Parkinson's Awareness Day to raise awareness about the disease. More than six million individuals live with Parkinson's disease (PD) worldwide. And the number is increasing due to an aging population. In most patients with PD, the causes are unknown. The characteristic symptoms such as stiffness and tremors are due to a loss of dopamine in the basal ganglia. As the disease progresses, nerve cells in the brain form aggregates that contain the protein alpha-synuclein. Unfortunately, when the patients get their diagnosis, the pathological changes have already evolved over decades, making the damage hard to rescue. Fortunately, ongoing research at MultiPark’s, Lund University opens for new discoveries, a journey from the innermost molecules of the Parkinson's brain to the patient’s everyday life.
Insights into toxic protein aggregation
Astrocytes are a cell type in the brain that supply nerve cells with substances necessary for their well-being. In collaboration with European colleagues, researchers at Lund University have gained an increased understanding of how astrocytes can contribute to neuronal cell damage as the disease progresses. They found that astrocytes from Parkinson's patients reacted differently compared to those from healthy people. The astrocytes responded to high concentrations of small pieces of alpha-synuclein by secreting inflammatory substances, which healthy astrocytes did not. Although astrocytes can break down smaller fibrils of alpha-synuclein, this is not the case for very large aggregates, similar to those observed in the later stages of PD.
Our findings highlight that for future treatments of PD we may have to act sooner rather than later. If the processes are too advanced and the aggregates too large, then it may not be possible to degrade these structures and reverse the progression of the disease," concludes Laurent Roybon, head of the study.
MultiPark’s biobank to study gene-environment interactions
Cell studies, similar to that of astrocytes, suggest that the cells of those with Parkinson's have a disturbance that causes them to behave differently. The critical question is to what extent this depends on our genes or on our lifestyle. MultiPark's researchers hope to gain more insight into the interaction between heritage and the environment with a new biobank. Through the biobank, they get access to the genetic profiles of 1,000 Parkinson's patients together with detailed information about their lifestyle and medical history.
Kajsa Brolin, a doctoral student at Translational Neurogenetics, uses the biobank in her doctoral dissertation. “It is fantastic that so many people have volunteered, half of all Parkinson’s patients in Skåne. This is unique and makes it one of the largest case-control studies in Sweden.”
One-fifth of all patients in the biobank had a relative with Parkinson's, despite few carriers of known mutations. Therefore, the researchers suspect that there is a significant genetic link to the disease, but that instead of a single gene, there may be an interaction between two or three genes.
Smart techniques open up for translational movement analysis
With animal models of the disease, it is possible to study how individual gene variants and environmental factors affect neuronal circuits of the brain. Studying abnormal movement patterns has long been the basis for Parkinson's research, both in terms of animal models and patients. But for a long time there has been a lack of tools to translate discoveries made in patients into rodents and vice versa. The recently launched project "eSCIENCE MOVES" will use artificial intelligence and machine learning to analyze movements in a more detailed way than before. In this way, one may detect more subtle deviations and link knowledge about abnormal movement characteristics between patients and rodents.
“At present, the assessment of PD-related movement disorders is based on human ratings that are not anchored to objective definitions. In the long run, our project will provide better definitions and improved assessment methods for clinical trials, as well as indispensable tools to unravel the circuit dysfunctions causing different types of motor abnormalities,” explains Angela Cenci Nilsson, MultiParks coordinator and leader of the project.
A new tool to manage treatment
Algorithms are also used in a new treatment tool developed by Professor and senior attending physician Per Odin in collaboration with Region Skåne hospital. With the tool "Manage PD", he hopes that more Parkinson's patients will receive the proper treatment at the right time in the course of the disease. If the doctor knows the patient, it only takes a few minutes to enter various facts. The system then suggests what the doctor should do: stop the current treatment, change the tablet treatment, refer to a Parkinson's center, or examine the patient for advanced therapy.
Acceptance is the key for maintained life satisfaction
Having access to the right treatment can be crucial for the quality of life of those who have Parkinson's. But there are also other factors that affect how satisfied the affected are with life. In-depth interviews with patients in the early stages of the disease reveal that acceptance creates the conditions for maintained life satisfaction. The study was conducted by Lina Rosengren, a doctor in rehabilitation medicine and a researcher at MultiPark.
Overall, MultiPark's ongoing research projects contribute to an increased understanding of the disease and to improving the lives of those affected by Parkinson's.
