|Title||Recent developments in narcolepsy research, an explanation for patients and the general public|
|Publication Type||Magazine Article|
|Year of Publication||2000|
|Authors||Siegel, JM |
|Magazine||Narcolepsy Network Newsletter|
|Full Text|| |
Narcolepsy is no longer a mysterious disease. In work reported this September, our group at UCLA and Mignot's group at Stanford independently identified abnormalities in human brains that pinpoint the cause of most human narcolepsy. We were able to acquire four brains of deceased people who had had narcolepsy, and our work was based on a comparison of these brains with the brains of twelve neurologically normal deceased people. There are many different kinds of cells in the brain, with each kind containing different chemicals. In our work, we found that the number of brain cells containing the chemical named hypocretin (also called orexin) was reduced by 85-95% in people with narcolepsy. We found that neurologically normal individuals have about 70,000 hypocretin containing cells, whereas the narcoleptic individuals have between 3,000 and 10,000 of these cells. The brain region where hypocretin cells are located is called the hypothalamus and is located at the base of the brain. We found that scar tissue (also called gliosis) was present in regions of the hypothalamus where hypocretin brain cells used to be. This indicates that the cells were present at birth and died later. It is likely that they died at or shortly before the time of symptom onset.
The cause of the death of the hypocretin cells is not entirely clear, but there are two possibilities. One is that a specific "poison" produced by the body or absorbed through the environment kills these cells. Parkinson's disease, another neurological disease caused by the loss of specific brain cells, can be triggered by ingested toxins, for instance. The second and more likely possibility is that the hypocretin cells are killed by the immune system, which confuses these cells with an infectious agent such as a virus. Other cells near where the hypocretin cells should have been appear to be normal; this indicates that whatever the cause of the cell loss, the hypocretin cells are targeted very specifically.
There are some differences between the findings of the two studies. Mignot's group concluded that all the hypocretin cells were absent in the hypothalamus of the two brains they examined, but we saw cells that had survived in all four of the brains we studied. Mignot's group also counted only 15-20,000 hypocretin cells in the normal brains they studied, compared to the 70,000 we saw. In addition, Mignot's group did not see scar tissue in the narcoleptic brains. However, we observed this scar tissue in all of the narcoleptic brains we examined. These differences are probably due to differences in the sensitivities of the techniques used in each laboratory. However, both groups are in basic agreement that hypocretin cell loss causes narcolepsy in humans. One problem that both of our groups faced, however, is that very few narcoleptic brains are available for study. Although animal work has been vital in unraveling the mystery of narcolepsy, we now must now have more human brains to study to progress further in our understanding of narcolepsy in humans. People with narcolepsy who will their brains to science can greatly contribute to our understanding of this disorder.
What does finding the cause of narcolepsy mean for people with narcolepsy? This discovery ends the 120-year search for the cause of this debilitating disease. It also has important implications for people with narcolepsy: