Is this the most important narcolepsy research news this year?

One of the problems with narcolepsy research is that drug companies like to focus on “big disorders” which if they can find a drug that will cure or help it, will make then billions. Unfortunately narcolepsy isn’t in that sort of category and as such people with narcolepsy do have to make do with what is available. While that isn’t going to change anytime soon one of the biggest problems facing medicine today, obesity, may be coming to the aid of narcolepsy research.

It’s probably fair to say that weight gain is one of the major problems for people with narcolepsy. Narcoleptic patients will often gain kilos even as they eat considerably less than an average person. Have you ever wondered why? Well researchers reporting in the October issue of Cell Metabolism, appear to have an answer. It seems a deficiency of orexin, a neurochemical that encourages hunger and wakefulness, may leave them with a lack of energy-burning brown fat.

The findings may lead to orexin-based weight loss therapies for those with narcolepsy and for the rest of us, too, according to the researchers. “Orexins are highly unusual in that they allow one to eat more and lose more at the same time,” explained Devanjan Sikder of the Sanford-Burnham Research Institute. “Orexin, a hormone produced in the brain, activates calorie-burning brown fat in mice. Orexin deficiency is associated with obesity, suggesting that orexin supplementation could provide a new therapeutic approach for the treatment of obesity and other metabolic disorders. Most current weight loss drugs are aimed at reducing a person’s appetite.” An orexin-based therapy would represent a new class of fat-fighting drugs - one that focuses on peripheral fat-burning tissue rather than the brain’s appetite control centre.

Since the best way to determine something’s function is to see what happens when it’s missing, Dr. Sikder looked at mice genetically engineered to lack orexin. These mice weighed more than their normal counterparts, but they actually ate less, suggesting that overconsumption was not the cause of their obesity. Rather, the orexin-deficient mice when fed a high-fat diet, failed to remove the extra calories as heat the way that normal mice (and people) do. Instead, they stored that energy as fat.

This finding prompted the team to look at the mice’s brown fat. Fat comes in one of two types: white or brown. White fat stores calories while brown fat burns them, generating heat in the process. There had been hints that orexins might influence body temperature, certainly many people with narcolepsy report temperature problems but it wasn't clear exactly how or why. What they found is that brown fat in mice lacking orexin didn’t develop properly at the embryonic stage. This shortage had lasting effects on energy expenditure and weight even in adulthood.

Taking the opposite approach, the researchers then gave the defective mice more orexin. With the hormone present, brown fat developed properly before birth and continued to be active into adulthood. What’s more, adding orexin to stem cells in a laboratory dish caused them to differentiate (specialize) into brown fat cells, creating more of this fat-burning engine.

“Without orexin, mice are permanently programmed to be obese. With it, brown fat is activated and they burn more calories,” said Dr. Sikder. “We’re now taking the next steps in determining how orexin - or a chemical that has the same effect - might be used in humans to therapeutically prevent or treat obesity.”

There are already ways of stimulating brown fat's production, but it isn't easy to do. For instance, more brown fat is produced when you spend a lot of time in the cold. The new findings suggest that orexin therapies might be useful for increasing brown fat and literally melting extra calories away. "One caveat is that orexin will increase your ability to stay awake," the researchers wrote, "although this is expected only under sleep deprived conditions." Sikder says it will now also be worthwhile to examine orexin-deficient people with narcolepsy to find out whether their brown fat activity is indeed compromised.
What does all this mean? Two things really. If this research can be replicated and it is found out that orexin can indeed act as a super slimming aid you can bet your last pound (money not weight) that a lot of research time will be spent on getting through the problems of getting orexin into the brain or finding a drug that mimics orexin in some way. The first company that can crack that will have a multi-billion dollar market to control in terms of weight loss. As a secondary effect a possibility to control narcolepsy by regular orexin or drug uptake could signal the beginning of the end of the problems with narcolepsy.
The second thing is that people with narcolepsy are very soon going to be in demand for research. You read it here first!

Please do realise that this isn’t going to be a quick answer; in fact if the “brown fat” hypothesis and orexin isn’t proven in humans it isn’t going to be an answer at all. If it is proven - and talking to a Stanford researcher those tests are under way at the moment - then a huge opportunity is on the horizon. This isn’t going to affect your life in this decade but profit is a great research motivator. It seems strange that something that many people with narcolepsy complain about – weight gain – could be the reason that research in getting orexin or an orexin like drug through the blood brain barrier is really funded.