Research in narcolepsy and hypersomnia is continually evolving, with new diagnostic tools and treatment options in development.
As our understanding of the biology of narcolepsy and hypersomnia evolves, other diagnostic tests and treatment possibilities develop. Although it can take some time for these to come in to regular use in the clinic, understanding where research is at and where is it going helps get an idea of the direction things are heading.
Making a diagnosis of narcolepsy or hypersomnia often takes many years, as even people with typical symptoms including cataplexy often find. Often health care providers don’t recognise the symptoms of narcolepsy, so there is still a lot of work to be done educating health care providers about narcolepsy and hypersomnia.
Diagnosing narcolepsy on an overnight sleep study: Whilst typically a multiple sleep latency test (daytime napping test) is used to diagnose narcolepsy in the sleep laboratory, Prof Emmanuel Mignot and his group at Stanford have looked at the overnight sleep studies of people with narcolepsy. They found that if someone goes in to REM sleep within 15 minutes on their overnight sleep study that is diagnostic of narcolepsy as the likelihood of that person having narcolepsy is 99.4%. However, this isn’t a very sensitive way of diagnosing narcolepsy as they found only 51% of people with narcolepsy had this finding. This original research was published in JAMA Neurology in 2013, but has now been replicated by other groups and in children. The most recent study, which is not yet published shows results more like I see in clinical practice, with only 7% of people with narcolepsy having this finding, but 99.2% of people with this finding having narcolepsy.
Sodium Oxybate (Xyrem) – time to response: Sodium oxybate (Xyrem) has just become available for use in Australia, and people are asking me lots of questions about it’s use. Things like, how long do I need to trial it for to see if it is going to help? Research just published in the Journal of Clinical Sleep Medicine helps to answer that question. They looked at 86 people with narcolepsy who had used sodium oxybate in a clinical trial, and determined how long it took for people to get the maximum response with reductions in cataplexy and sleepiness symptoms. For cataplexy, by 25 days, 50% of people had a 50% reduction in the number of cataplexy attacks. For sleepiness, by 37 days, 50% of people had a 20% reduction in sleepiness, and as shown in the graph below, 50% of people had reached their maximum reduction in sleepiness by 106 days – just over 3 months.
JZP110: Jazz Pharmaceuticals are developing a new drug for the treatment of narcolepsy. It is a combined dopamine transporter (DAT)/norepinephrine transporter (NET) inhibitor, currently labeled JZP-110 (previously known as ADX-N05). So far, they have tested it in people with narcolepsy. In one trial presented at Sleep 2015, of 90 people with narcolepsy, 47% reported being either very much or much improved taking JZP110. Jazz also reported clinical trial data suggesting that the simultaneous antagonism of both DAT and NET may be more effective than drugs that have just one of these actions and don’t result in as much release of wake-promoting neurotransmitters.
Pitolisant: Histamine is thought to be one of the key neurotransmitters involved in the regulation of alertness and wakefulness. Pitolisant is a histamine 3 receptor (H3R) inverse agonist, and is the first agent that acts on histamine to be evaluated by health authorities for the treatment of sleepiness. So far, the majority of clinical trials have been in narcolepsy, but as histamine is thought to be important in idiopathic hypersomnia (IH), it may have a significant effect in people with IH. Final regulatory approval for the use of pitolisant in narcolepsy is pending in Europe, so it may be available in Europe soon as a narcolepsy treatment. Previous work published in The Lancet in 2013 had shown pitolisant had similar effects to modafinil on sleepiness in people with narcolepsy.
Orexin receptor structure and orexin receptor agonists: As narcolepsy with cataplexy is a disorder of orexin deficiency, with orexin secreting neurones being destroyed by an auto-immune process, the ideal treatment would be orexin replacement. However, this is difficult as the receptor structure hasn’t been well characterised and it is difficult to get the required drugs in to the brain, across the blood-brain barrier. However, recent work published in Nature has been able to work out the structure of the human orexin 2 receptor, and how to bind drugs to it that could then either stimulate or inhibit the receptor. Drugs that stimulate the orexin receptor (agonists), would be an ideal treatment for narcolepsy with cataplexy, that would address all of the symptoms by replacing the effects of missing orexin. From this research, other groups have now already developed orexin receptor agonists, and are moving on to looking at how to get these drugs in to the brain in the required concentrations. We hope that in 5-10 years we will have orexin receptor agonists available in the clinic as treatment for narcolepsy with cataplexy.
Related posts & links:
- What is narcolepsy?
- Managing narcolepsy as a team
- Narcolepsy Support Australia
- Stanford Center for Narcolepsy
- Julie Flygare’s blog on narcolepsy
- Hypersomnia info
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