Clearing the Sleepy, Dreamy Fog That Shrouds Narcolepsy

2010-02-18 | |
Last updated: 2010-02-18
narcolepsy immune disease and fatigue

As children, many of us have played the game “Which one of these things does not belong?” For the benefit of those who do not know the game, it is straight forward – you simply pick the item from a list that is different from the rest.

If you were provided the following list, Multiple Sclerosis, Type-1 Diabetes, Narcolepsy, Rheumatoid Arthritis, Lupus, which one would you choose? If you are thinking that all of these except Narcolepsy are related diseases, you would be wrong. It’s a trick question because all of the conditions are immune system disorders. It is just that for Narcolepsy, scientists have only recently confirmed the relationship.

Narcolepsy is a sleep/wake disorder in which those with the condition experience abnormally high levels of daytime fatigue and a tendency to fall asleep with little or no warning during the day. Sometimes those with the condition may even dream while awake. At night, those with the condition will suffer from disturbed sleep patterns though they will often fall asleep very quickly. In some cases, people with the condition can also suffer from sudden muscle weakness that ranges from mild severity to levels that can cause a person to collapse.

Often a source of parody in comedy where the symptoms are almost always exaggerated, the condition is certainly deserving of more understanding than it receives. The lives of people with even moderate forms of the disease are dramatically affected by it. Imagine not being able to drive, not being able to hold a job where alertness is required and needing to be escorted when outside the home in the more extreme cases. These are the not-so-amusing aspects of this condition.

In the population, as many as one in 2000 people suffer from Narcolepsy and there are more than 3 million afflicted by the condition worldwide. In the US, the number of people with the condition is 200,000. Unfortunately, less than 1 in 4 of those with the condition has been diagnosed as having it. The symptoms often lead to misdiagnosis of depression or insomnia and with misdiagnosis comes incorrect, insufficient or ineffective treatment.

Given that the condition has not been well understood, the recent confirmations that Narcolepsy is an immune system disease means that the development of better tests and treatments can now begin. Though the theory for Narcolepsy being an immune disorder has been around and building for some time, assembling the argument has been a long, involved task.

Researchers at the University of Washington began analyzing previous research prior to 2007 to identify whether environmental factors could contribute to development of the condition. Environmental factors are thought to be a contributor to many immune system diseases so investigating this approach was based on a theory involving immune disruption.

Sometime later, in behavioral research at Radboud University Nijmegen Medical Center in the Netherlands, scientists found that 23% of people with Narcolepsy also suffered from eating disorders. This compares to less that 1% of the general population. Given the current understanding of brain hormones, this information makes sense because the same hormones that control our ability to be awake also control appetite and food cravings. Thus, a lack of these specific hormones or cells to respond to these hormones would result in both of the symptoms seen in Narcolepsy and eating disorders.

Subsequently, based on similar sleep disorders being observed in both Narcolepsy and  Parkinson’s patients, research at the University of California at Los Angeles determined that these diseases were related.  Patients with Parkinson’s were observed to have levels of sleep disturbance that increased as the number of brain cells of a specific type decreased. In some cases, patients were observed to lose as many as 60% of these specific brain cells.

Later research from Sungkyunkwan University School of Medicine in Korea confirmed this with the discovery that the density of gray matter in the brains of Narcolepsy patients is less than for the general population. In particular, the reduction in brain cells was observed in areas of the brain related to attention, memory and consciousness. These findings support the theory that people with the condition have suffered a loss of very specific brain cells.

A key culprit in the death of cells is often the immune system so researchers at the University of Stanford explored this theory. The study involved analyzing the genes of 1800 people with a known genetic abnormality that affects how the immune system determines the difference between cells of the body and foreign materials. Of the people whose genes were used in the study, 800 had Narcolepsy and in these individuals, scientists isolated a common gene. Subsequently, based on knowledge of previous research, the scientists correlated that gene to involvement with the immune system.

With this, scientists had determined that the loss of brain cells that causes Narcolepsy is the result of the immune system selectively attacking the brain. This makes the condition similar to Multiple Sclerosis in terms of the immune system attacking brain cells.

With the mystery cause of the disease now identified, the next phase in research can now proceed. As with other immune disorders, scientists can try to determine ways to block the immune system from attacking these cells. They can also attempt to use gene therapy to deactivate the specific genes before external factors turn on the disease. They can also explore the use of stem cells to replace the brain cells that have been destroyed. In short, the future for those suffering from the disease certainly seems a little less foggy.

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