New cell type contributes to better understanding of ALS

The causes of severe muscle disease ALS are still unknown. Now, researchers from the Karolinska Institutet and the KTH Royal Institute of Technology, among others, have looked at a type of cell in the blood vessels of the brain that may explain the disease’s unpredictable origins and dynamics. The results indicate a hitherto unknown connection between the nervous and vascular systems. The study, which is published in Nature medicine, has potential implications for early diagnosis and future treatment.

ALS (amyotrophic lateral sclerosis) is a neurodegenerative disease of the motor neurons that eventually causes muscle atrophy, paralysis and death. There is currently no cure.

The cause of ALS is only understood in 5 to 10 percent of patients with an inherited form of the disease. To aid in its early detection and develop effective therapies, researchers are eagerly seeking a clearer picture of the pathogenesis of the disease.

ALS patients show great variability in age at onset, non-motor symptoms, and survival. In recent years, research has shifted attention from neurological explanations to these differences and has focused, for example, on the cerebrovascular system, which provides oxygen and nutrients to brain tissue.

Researchers at Karolinska Institutet, KTH Royal Institute of Technology, SciLifeLab, Imperial College London and Umeå University have now investigated whether there is a possible link between perivascular fibroblasts and the timing of onset of disease and survival.

Studies in mice with ALS have shown that genes for perivascular fibroblasts were already active at an early asymptomatic stage of the disease and months before the onset of neuronal damage.

The researchers then examined the levels of a large number of potential marker proteins in the plasma of 574 patients newly diagnosed with ALS and 504 healthy controls from four countries.

Their results suggest a correlation between high levels of the SPP1 protein marker for perivascular fibroblasts and an aggressive disease process and shorter survival. This is the first time that a connection between the vascular and nervous systems in sporadic ALS has been observed.

“It is exciting to see how the results of our protein profiling could be linked to the long range of cellular and molecular analyzes we have performed and reveal the identified association with disease progression,” says lead author Anna Månberg, researcher in the department. of Protein Science, at KTH and SciLifeLab.

“Our results indicate that vascular events are a factor in the heterogeneity of the disease and may improve our knowledge about early stage ALS,” says the latest and lead author of the study, Sebastian Lewandowski, researcher in the Department of Neurosciences clinics and the Karolinska Molecular Medicine Center. Institutet. “Further studies are now needed on the mechanisms of vascular disease for better prognostic tools and future treatments.”

The research was funded by the Olle Engkvist Foundation, the Ulla-Carin Lindquist Foundation for ALS Research, the Swedish FTD Initiative and others, and received strategic support from the Knut and Alice Wallenberg Foundation and the Erling-Persson Family Foundation for the KTH Center for Applied Precision Medicine (KCAP).

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