Study traces cystitis contribution to neurological disorder MSA

Research from KU Leuven and Van Andel Research Institute shows that after inflammation of the urinary bladder there is an increased risk of developing multiple system atrophy (MSA). MSA is a rare, aggressive neurological disorder. As a result of a bladder infection, pathogenic clumps of the protein α-synuclein form in the bladder and can migrate to the brain. The accumulation of the protein in the brain damages brain cells and can lead to MSA. Thanks to this research, published in Acta Neuropathologica , a way to treat MSA at its source, instead of just alleviating the symptoms, can be found.

Multisystem atrophy (MSA) is a neurological disorder that affects about 1 in 25,000 people. In patients with MSA, nerve cells and certain areas of the brain are gradually affected and eventually die. This causes damage to the autonomic nervous system, causing patients to experience problems with breathing, digestion, bladder control or blood pressure regulation, among other things. It has already been shown that the accumulation of the protein α-synuclein in the brain causes the breakdown of brain cells, but the cause of this clumping was unknown until now. Research by KU Leuven and Van Andel Research Institute shows that bladder infections can be a trigger for the accumulation of α-synuclein and thus contribute to the development of MSA.

(Bladder) inflammation as a trigger
α-synuclein is present in everyone’s brain and contributes to good communication between brain cells. When our body becomes infected by a bacteria or virus, for example, the immune system will also produce α-synuclein to ward off the infection. Excessive production of α-synuclein can cause clumping, which damages cells and eventually causes them to die.

Now that we know that bladder infections, or infections in general, play a role in the development of MSA, we can investigate how we can target the clotting mechanism of α-synuclein to treat the disease at its source.

Professor Wouter Peelaerts

Led by Professor Wouter Peelaerts of KU Leuven and Professor Patrik Brundin of Van Andel Research Institute, bladder infections have been shown to increase the risk of developing MSA by three times. This relationship was further investigated by measuring the concentration of α-synuclein in human samples of the urinary bladder and mice with cystitis. Due to the bacterial infection of the urinary bladder, the immune system produces α-synuclein. At a high concentration, protein clots can form, which migrate to the brain via the nerve cells of the bladder. If the clots reach the brain, they can affect brain cells, causing the nervous system to malfunction, eventually leading to MSA.

“We opted for bladder infections in this study, because many patients with MSA report that they regularly suffer from this, even in the years before their diagnosis. However, the link between the two has never been investigated. This research shows that a bladder infection, which seems banal at first sight, can have far-reaching consequences. Although this study focuses on one specific inflammation, it cannot be ruled out that other inflammations have the same effect. After all, the production of α-synuclein is present in every inflammatory reaction,” explains Professor Peelaerts.

Intervene at the source
MSA is an aggressive condition that causes patients to systematically require more and more help. For the time being, doctors can only reduce the symptoms, but the disease itself cannot be cured. “Now that we know that bladder infections, or infections in general, play a role in the development of MSA, we can investigate how we can intervene in the clotting mechanism of α-synuclein to treat the disease at its source,” says Peelaerts.

“Everyone has an infection from time to time, yet only a limited number of people develop MSA. Further research is needed to find out exactly what causes one patient to be more predisposed to MSA than another. There may be a genetic explanation for this,” concludes Peelaerts.