In the late 1990s, three different research groups determined that a neuropeptide system located in the brain, specifically in the hypothalamus, has a system that balances or dictates the body’s sleeping habits. This was then known as the hypocretinergic system. These systems pump a substance called hypocretins or orexins. Just until last decade, narcolepsy was credited to the deficiency of orexin which means Narcolepsy develops when there isn’t enough orexins to keep a person awake. In fact, to this day, people with Narcolepsy don’t have orexins in their spinal fluid (Black, 2005; Nishino, 2005).
More studies have been made though and after the DNA of canine revealed that the Narcolepsy is indeed in the DNA, great progress have also been made on humans (Reily, 1999). Many researchers now believe that the disease is developed when there is an irregularity in the structure and nature of a hypocretin neurons, a kind of nerve cell (Nashino et al, 2009). These are found in the brain, within the hypothalamus. This is the same cell that supplies a transmitter called hypocretin. When the hypocretin aren’t functioning as efficiently as intended, it causes people to sleep more and abruptly.
Several experiments have already been conducted to know more about hypocretin neurons. However, these experiments involved dogs. It was discovered that the changes in the gene prompted the brain on three different dog breeds. Hypocretin may also play a role in other sleeping disorders such as insomnia (Ritchie, 2010; Sakurai, 1998).
Led by Dr. Emmanuel Mignot (1997), a team of researchers from the Stanford University Center for Narcolepsy in Palo Alto, California, the group manipulated the gene and injected it to a Dachshunds, Labrador retrievers and Doberman pinschers. Each dog breed showed different effects. Some showed sporadic day time sleepiness and some showed wakefulness.
If these results are consistent with humans, genes may not be the only factor in Narcolepsy. The body make up will most likely dictate how the body will react to a specific stimulus such as hypocretin stimulus and how the body develops highly depend on diet and overall health.
Researchers also believe that people may have less hypocretin neurons because the autoimmune system attacks the brain cells. What causes the attacks is also unknown but it does happen.
Immune system, however, is one of the many functions of the body is that is highly dictated by external variable such as diet, body resistance and overall health. When the brain gets attacked, it is the hypocretin that gets destroyed. It is, however, important to note that narcolepsy has never been proven as an autoimmune disease. This will be discussed further below.
There are children that are reported to have Narcolepsy but most cases happen between the ages of 15 and 25 (Chabas et al, 2003; Dauvilliers, 2001). Noticeably, it develops during the time when people have already been great affected by external stimulus such as food. This could further prove that the environment really play a big part in the development of Narcolepsy.
Researchers believe, though, that even more cases go unreported, undiagnosed and untreated.
There have been estimates that between 12 percent and 35 percent of Americans carry the Narcoletpic gene but less than one percent develops into a full disorder. It is also true that it may be genetically connected but it doesn’t mean that every person in the family is Narcolepitc (NINDS 2011). In fact, generations might pass before someone else in the family gets the disorder (Maret et al, 2005).
There also been a lot of indication that suggest Narcolepsy is connected to some irregularity in the autoimmune system, very similar to multiple sclerosis. There are some theories that dictate that people who suffer some kind of trauma are most likely to develop Narcolepsy changes happen within the nerve cells in the brain. However, many of the research need additional data. There are very few conclusions that would categorically conclude the connection.
There was one study in 1980 that showed high HLA among those with Narcolepsy. Since then, other groups have conducted independent studies to examine the presence of the connection between HLA and Narcolepsy (Klein, 2000). The most evident sign of narcolepsy on the different groups showed that an average of 90 percent of the sample population had unequivocal cataplexy. There is also a remarkably low association between people with Narcolepsy and absence of Cataplexy (Deloumeau, 2010; Juji et al, 1984).
Researchers at the University of Lausanne, Switzerland, conducted one of the most definitive studies that linked auto-immune system or auto-antibodies to narcolepsy. The immune system usually is able to identify anything that is foreign and attacks it. It is the first line of defence of the body. When there is an abnormality in the autoimmune system, it is unable to identify what is foreign and what naturally belongs to the body (Chabas et al, 2003; Dauviliers & Tafti, 2006).
The autoimmune system irregularity causes it to attack a natural protein called Trib2. This causes paralysis in the body which causes it to collapse.
A 2006 study determined that there is higher possibility of Narcolepsy being passed on to male first-degree relatives (parents or sibling) (Kroeger & Lecea, 2009).. In fact it is 105 percent higher than the possibility of Narcolepsy being passed on to other relatives. For female fir-degree relatives, there is 54 percent higher possibility (Dauviliers & Tafti, 2006).
There is also a study that concluded a 20 to 40 percent higher chance of people developing Narcolepsy when there is already someone in the family that has the disorder.
In another study, however, it is determined that there is only about one to two percent of all Narcolepsy reports that prove it runs in the family. The average is slightly higher among identical twins with ten to twenty percent (Dauviliers & Tafti, 2006).
This is the primary reason there is a prevailing belief that Narcolepsy is triggered by both genes and environment. Those with irregularity in the Hypcretin are most prone to developing Narcolepy but it takes other external agents for the disorder to mature.
The lack of vigilant interest to conclusively determine the causes of Narcolepsy is primarily due to the absence of life threatening effects. Aside from possible bumps or accidents a person with Narcolepsy might encounter during sleep attacks, no other reports remotely threatens the life of those who have it.
However, the discovery on the connection between Narcolepsy and the autoimmune system might change this perspective. The antibodies are the first line of defence of the body. When it starts attacking what naturally belongs to the body. Future studies must be pursued to further understand whether the attacks are limited to Trib2 and what are the characteristics of Trib2 that makes the antibodies unable to identify it as an organic part of the body.
There is also a need to explore the external stimulants that cause the body to develop Narcolepsy. Based on the studies, not everyone that has the Narcoleptic gene will develop Narcolepsy. Is it diet? General physical health? Certain environment triggers? Understanding what these factors are might be the key in preventing the disorder from fully developing.