A rare and fatal brain disorder with no available treatment or cure. One that attacks the nervous system, balance, and the ability to move.
This is the reality for patients with multiple system atrophy (MSA) – a disease that in many ways resembles Parkinson’s disease, but which strikes earlier and progresses more aggressively.
In a new study, researchers from the University of Copenhagen and Bispebjerg and Frederiksberg Hospital examined brain tissue from MSA patients to better understand why the disease progresses so rapidly.
The brain’s immune cells, known as microglia, appear to play an important role.
“We expected to see a very active immune system in the brain of patients with MSA, because the disease is so aggressive. That is also what we see in patients with Parkinson’s. But we found the opposite. It appears that the brain’s immune cells are dozy or exhausted, as if they have lost their ability to respond – at least in the later stages of the disease,” says Konstantin Khodosevich, Professor at the Biotech Research and Innovation Centre (BRIC) at the University of Copenhagen.
Normally, immune cells function as a kind of garbage collectors that clear away waste products in the brain, such as accumulated proteins and dying cells. But if immune cells fail to do their job, this can cause diseases such as Parkinson’s and MSA.
“We know from other studies that the immune system is very active at the beginning of the disease. Therefore, we have a theory that the immune system may have been overactivated, causing the immune cells to become exhausted. And if the immune cells are not doing their job, the disease can develop more easily,” says Susana Aznar, research leader at Bispebjerg and Frederiksberg Hospital and co-leader of the study.
The researchers emphasize that further studies are needed to clarify whether an overactive immune system can exhaust immune cells.
In the study, the researchers analyzed brain tissue donated from three groups: patients with MSA, patients with Parkinson’s disease, and individuals without neurological disease.
The researchers used an advanced method known as single-cell RNA sequencing to analyze individual cells established by Konstantin Khodosevich. This method makes it possible to map the genes in each cell, even though the samples come from deceased patients.
“We take a very small piece of brain tissue the size of a fingernail and dissolve it into thousands of individual cell nuclei, which we analyze one by one. This allows us to see exactly what is going on in each individual cell type. It gives us a snapshot of what has happened in the brain at the end of the disease process,” explains first author Rasmus Rydbirk, previously Postdoctoral Researcher at BRIC (now bioinformatician at SDU).
In total, the researchers analyzed more than 117,000 cells and several thousand genes per cell. This enabled them to create a detailed “map” of the brain’s cell types and their condition across the different patient groups.
This is how the researchers became aware of the immune cells that appeared to behave differently in patients with MSA.
It is still too early to use the findings clinically, but the results provide an indication of where to look for potential treatment for MSA.
“MSA is a disease we know very little about, but our study shows that it is interesting to further investigate the role of microglia to see whether this could be a potential target for future medical treatment,” says Susana Aznar.
The Danish association for Multiple System Atrophy (Landsforeningen Multipel System Atrofi) welcomes the new research:
“It is devastating to be diagnosed with a fatal disease for which no treatments exist. That is why it is incredibly important that research into MSA is being carried out, so that we can better understand why the disease arises. As research is progressing in many places, it gives hope that in the future it may be possible to find a treatment or a cure,” says Chairperson Inge Vium.
Read the study ”Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy” .
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MSA
Multiple system atrophy (MSA) is a rare brain disease that in many ways resembles Parkinson’s disease.
MSA attacks the autonomic nervous system and can affect balance, the ability to move, and cause problems with urination, potency, and blood pressure.
The disease is chronic, and there is no treatment or cure. The average age at symptom onset is 55-60 years.
Sources: Susana Aznar, Landsforeningen Multipel System Atrofi , The Danish Parkinson’s Association
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How the researchers conducted the study
In the study, the researchers analyzed tissue samples from seven patients with MSA, 12 with Parkinson’s disease, and ten individuals without neurological disease. MSA is a rare disease, and the number of available brain samples is therefore limited. This reduces statistical power, even though the data resolution is high.
The samples were taken from the striatum, a region of the brain that is important for our ability to move and is affected in patients with MSA and Parkinson’s disease.
The researchers analyzed the tissue samples using single-cell RNA sequencing, which makes it possible to see which genes are active in individual cells – even if they originate from deceased patients.
By comparing the different patient groups, the researchers were able to see what stood out: Immune cells in the brain called microglia appeared to be more inactive in MSA patients than in those with Parkinson’s disease. However, the study does not establish cause and effect.
Because the brain tissue was donated after death, the analysis does not provide a picture of the entire disease course in patients with MSA but instead offers a detailed snapshot of what happens in the brain late in the disease.
Nature Communications
Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy
15-Apr-2026
A.A.M. is currently employed at Lundbeck A/S, the remaining authors declare that they have no competing interests.