Genetic evidence has been uncovered suggesting that narcolepsy is an autoimmune disease, confirming the long-held suspicions of many experts. A team from Stanford University School of Medicine, US, led by Dr Emmanuel Mignot, recently showed that a specific type of immune cell known as a 'T-cell' is involved in the disorder. The research appeared in the online version of the journal Nature Genetics, and should aid in the development of better treatments for the disorder. It could also help immunologists to understand other, more prevalent autoimmune disorders such as juvenile diabetes and multiple sclerosis.
Narcolepsy affects roughly one in 2000 people and is characterised by poor night-time sleep patterns, extreme daytime drowsiness leading to 'sleep attacks' and 'cataplexy' where strong emotions such as anger, surprise or laughter can trigger an instant loss of muscle strength, sometimes causing the patient to collapse. There is currently no cure.
In the 1990s Mignot and others identified the root cause of the condition - people with narcolepsy were found to be deficient in a hormone called hypocretin that 'promotes wakefulness'. Later they showed that patients were actually missing the brain cells that produce this hormone. Now it seems that the immune system's 'foot-soldiers', or T-cells, may actually cause the condition by attacking the sleep centres of the brain that make hypocretin.
'For a long time, people have suspected narcolepsy had something to do with the immune system - that it was killing cells that produce hypocretin', said Mignot, director of Stanford's Center for Narcolepsy. He added: 'But there hasn't been direct proof. Our discovery clearly shows narcolepsy is an autoimmune disease.'
The immune system differentiates between 'foreign' and 'self' cells using human leukocyte antigen (HLA) and recent studies have shown that more than 90 per cent of narcolepsy patients carry a variant in the HLA gene. The Stanford team conducted whole genome scans of 1,800 people carrying one such variant, and 800 of this group also had narcolepsy. One variation in particular, specific to a gene belonging to T-cells was present in narcoleptic patients and Mignot believes that the HLA and T-cell variants interact in a way that kills hypocretin cells (although they did not determine the exact mechanism).
'We're now getting the main pieces of what's happening in narcolepsy,' said Mignot. 'What's most satisfying to me is that we're bringing this story to a close and that we can use narcolepsy as a model for other diseases.' He continued: 'I'm sure immunologists are going to be very excited. If we can work out what happens specifically in patients with narcolepsy, we'll be able to better understand the role of T cells in other autoimmune diseases that are more complicated and difficult to detect.'