2024-01-16 01:44:01
Saarland University: new findings on the genetic causes of Parkinson’s disease
Saarbrücken, January 15, 2024
A team of scientists led by Prof. Rita Bernhardt from Saarland University has been working since 2020 to better research the development of Parkinson’s and to derive approaches for new, causal therapies. In their current work, the scientists show that in genetically predisposed Parkinson’s patients, additional changes in cytochrome P450 genes lead to the development of the disease. These genes are responsible for the production of enzymes that control important metabolic processes in the body. The research was carried out by Dr. Rolf Schwiete Foundation financially supported.
Parkinson’s disease is the second most common neurodegenerative disease, affecting around ten million people worldwide. Research groups around the world are working intensively to better understand the development and progression of the disease and to derive new treatment methods from this.
Scientists around the Saarbrücken biochemist Prof. Rita Bernhardt and the neurologist Prof. Marcus Unger (formerly neurology at the University Hospital in Homburg, UKS; now chief physician at the SHG Kliniken Sonnenberg in Saarbrücken) and Gudrun Wagenpfeil (medical biometry, Epidemiology and Medical Informatics, UKS). Your research study on the causes of Parkinson’s disease, which started as a pilot project in 2020, was continued until the end of 2023 by Dr. Rolf Schwiete Foundation financially supported. The scientists’ approach differs from the research of other laboratories and clinics in that, for the first time, the role of a large group of proteins – the so-called cytochrome P450 proteins – is examined, which regulates very different reactions in metabolism. It is investigated how changes in the underlying genes influence the development and expression of Parkinson’s disease.
“It is known that on average around 15 percent of all Parkinson’s patients have a genetic predisposition – in young Parkinson’s patients it is even up to 25 percent,” says Rita Bernhardt and explains: “Patients with a genetic predisposition have changes in one or more of around 20 so-called ‘Parkinson genes’. However, some people with the same genetic predisposition do not develop the disease, and the reason for this is completely unclear.
The scientists investigated this question in their most recent publication, published in August: Using freely accessible data from the Parkinson’s Progression Markers Initiative (PPMI), they took a closer look at the biodata of people with a genetic predisposition and focused on one person in particular large gene family: the cytochromes P450. This includes 57 genes that are responsible for the production and function of enzymes in humans, which control important metabolic processes in the body. The scientists had already demonstrated the special role of the cytochrome P450 genes in the development of Parkinson’s disease in a previous publication.
In their current work, the scientists analyzed the above-mentioned 57 cytochrome P450 genes from genetically predisposed people with and without symptoms of Parkinson’s disease. It turned out that in addition to the genetic predisposition, changes in various P450 genes were overrepresented up to tenfold in the sick people. “This means that people with a genetic predisposition become ill if they have an additional change in one of the P450 genes,” explains Rita Bernhardt. “In contrast, people with a genetic predisposition who do not carry a mutation in one of the P450 genes remain without symptoms.”
The P450 gene family plays a prominent role in numerous metabolic pathways in the human organism, including those that are involved in the biosynthesis of so-called eicosanoids. These act as immune modulators and thus regulate inflammatory processes in the body. The researchers also identified the particular importance of P450 genes, which are involved in vitamin A and vitamin D metabolism as well as cholesterol breakdown in the brain. »This means that the causes of the disease in these cases can be traced back to diverse combinations of gene changes, which is also supported by the very individual characteristics of the disease. Nevertheless, defined metabolic pathways – such as the synthesis and breakdown of immunomodulators or #cholesterol – obviously play a particularly important role,” explains Prof. Rita Bernhardt.
Since the study linked the causes of Parkinson’s disease to defined changes in specific P450 genes, further research can now be carried out to analyze the exact effects of these genetic changes. »On this basis, experimental groups can find out what influence the respective changes in the genes under investigation have on their function. This can then be used to develop starting points for hopefully causal therapies,” says Rita Bernhardt. The first interested parties and cooperation partners for this further work have already been found.
Publication in Frontiers in Pharmacology, August 4, 2023, more…
The research project by the team led by Prof. Rita Bernhardt and Prof. Marcus Unger on the causes and treatment of Parkinson’s disease started as a pilot project in 2020 and was run until the end of 2023 by Dr. Rolf M. Schwiete Foundation, Mannheim, financially supported with a total of almost 300,000 euros. More …
The Parkinson’s Progression Markers Initiative (PPMI) was launched in 2010 by the Michael J. Fox Foundation and a core group of scientists and industry partners to find urgently needed biological markers for the onset and progression of Parkinson’s disease. Since then, PPMI has engaged thousands of partners and initiated online patient data collection. Analysis of the freely accessible dataset and available library of biospecimens deepens the understanding of the #disease and enables the planning of dozens of therapeutic studies. More …
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