Spatial omics paving the way for better diagnosis and treatment of Parkinson's disease

Every year, more than two thousand Swedes are diagnosed with Parkinson's disease, a chronic movement disorder that worsens over time and increases the risk of developing dementia. Parkinson's is caused by the slow death of nerve cells that produce dopamine, but with the right treatment, symptoms can be eased. Unfortunately, there are other neurological diseases with symptoms similar to Parkinson's dementia, for example Lewy body dementia, which makes it difficult for physicians to establish the correct diagnosis.

“There is a great need for methods to differentiate the various parkinsonian-like dementias already at an early stage. With financial support from the Swedish Research Council, we are running an interdisciplinary, six-year project, where we use Spatial omics technologies with the aim to map the underlying mechanisms, which can in the long run provide us with the necessary biomarkers. In another project, funded by the Swedish Research Council and the Brain Foundation, we are studying the long-term effects of treatment of Parkinson's disease” says Per Andrén, Professor of Mass Spectrometry Imaging.

Parkinson's disease is currently treated with L-Dopa, a precursor to dopamine that initially gives good results, but the effect deteriorates over time and can cause increasing, involuntary movements. In a highly recognized article in Science Advances, Per Andrén shows that brain tissue from a Parkinson's model affected by such side effects contains excessive levels of L-Dopa and 3-O-methyldopa, a product that is formed when L-Dopa is broken down into dopamine. A finding that is expected to add new and important knowledge to the treatment of advanced Parkinson's disease.

“Healthcare needs tools against Parkinson's, and in an article in Nature Communications, we recently presented results showing how altered prosaposin levels correlate with motor impairments in Parkinson's patients. Using mouse models, we further noted that a deficiency of PSAP leads to behavioral changes and a reconfiguration of lipid metabolism in the brain, opening the doors to an exciting future for research in our field,” concludes Per Andrén.

FACTS SPATIAL OMICS

• Is a relatively young area of technology that with powerful instruments and large-scale analysis in tissue samples, generate data that constitute key tools for research in fields such as cancer, immunology and neurology.
• SciLifeLab provides a national resource for Spatial Omics bringing together several frontline environments, among them Per Andrén's laboratory for Spatial Mass Spectrometry at Uppsala University.
• SciLifeLab Spatial Omics offers access to technology for spatially resolved RNA, protein and small molecule analyses of histological tissue sections. The platform comprises expertise in Spatial Proteomics • Spatial Transcriptomics • Spatial Mass Spectrometry.
• In the interdisciplinary project funded by the Swedish Research Council, Per Andrén's research group collaborates with five research groups led by Mats Nilsson (Stockholm University), Emma Lundberg and Lukas Käll (KTH), Per Svenningsson (KI) and Luke Odell (Uppsala University).

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• Research in Spatial Mass Spectrometry at Uppsala University

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text, Magnus Alsne, photo: Mikael Wallerstedt