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Narcolepsy may be caused by the body attacking itself

Health and diseases
Researchers from DTU and the University of Copenhagen are now pointing out that narcolepsy is an autoimmune disease. This may be important to future treatment of this chronic disorder.

Between 2,500 and 3,000 Danes suffer from the sleep disorder narcolepsy—which is characterized by a sudden and overwhelming urge to sleep. The disorder is typically treated with drugs which stimulate the central nervous system.

It has long been assumed in medical science that narcolepsy is an autoimmune disease, but final proof of this has been lacking.
Now, researchers from DTU Health Technology and The Faculty of Health and Medical Sciences at UCPH have—together with Rigshospitalet (Copenhagen University Hospital)— found further evidence that the assumption holds true. The new research findings have been published in the scientific journal Nature Communications.

“As the first in the world, we’ve discovered that the body is able to trace some special neurons which play a key role in narcolepsy. Seeing that this is the case, the body will also be able to attack these neurons in a targeted manner via an autoimmune reaction,” says Professor Sine Reker Hadrup, DTU Health Technology.

The immune system is designed to recognize viruses and bacteria. When the cells of a disease are autoreactive— which is a characteristic feature of an autoimmune disease—this means that the immune system recognizes the body’s own cells and attacks them. In the majority of people with narcolepsy, the neurons which produce hypocretin—and thus control our waking state—have been destroyed.

“We’ve found autoreactive CD8 T cells in the blood of narcolepsy patients. This means that the cells recognize the neurons which produce hypocretin, which regulates wakefulness. It’s not a proof that they’re responsible for killing the neurons. But it’s a very important step in the process. Now we know what the cells go after,” says Associate Professor Birgitte Rahbek Kornum, Department of Neuroscience, University of Copenhagen.

CD4 and CD8 T cells typically have to interact in order to kill other cells, for example the neurons that produce hypocretin. In 2018, autoreactive CD4 T cells were ascertained in connection with narcolepsy, but this new study from DTU and UCPH shows for the first time the presence of CD8 T cells which can recognize hypocretin neurons. The researchers find a higher presence of such autoreactive CD8 T cells in patients with the most common form of narcolepsy than in a comparable group of healthy subjects.

Healthy subjects also had autoreactive cells
In the study, the researchers studied and analysed blood samples from 20 narcoleptics. In addition, they analysed blood samples from a control group of 52 healthy persons. The researchers found autoreactive CD8 T cells in nearly all 20 narcoleptics. But the researchers did not only find autoreactivity in the subjects with narcolepsy.

“We also found autoreactive cells in the healthy subjects, but these cells probably haven’t been activated. It’s something that we’re beginning to see more and more in autoimmunity—that all persons have latent autoimmunity—it’s simply not activated in everyone. The next big mystery will be to find out what activates the autoimmunity,” says Birgitte Rahbek Kornum.

According to Birgitte Rahbek Kornum, the discovery of autoreactive cells in healthy persons also emphasizes that there must be something that triggers narcolepsy and initiates the autoreactivity. It is still not completely clear what causes the disease. It is presumed that it is a combination of genetics, autoreactive cells, and a type of trigger that causes the onset of the disease, for example a viral infection.

Today, there is medicine against the disease, but the new research results may pave the way for even more effective treatments.

“Our study shows that the immune system in most subjects from both the patient group and the control group was able to recognize components from the neurons that produce the sleep neurotransmitter hypocretin. But we could also observe that the immune system in narcolepsy patients was especially in alert mode,” says Sine Reker Hadrup and continues:

“So even though we still don’t know why a few persons develop narcolepsy, while the majority don’t suffer this sleep disorder, there are by now really many factors indicating that narcolepsy can be characterized as an autoimmune disease.”

The researchers expect that these findings will entail that—in future—there will be more focus on trying to develop narcolepsy treatments based on drugs that regulate the immune system.