Research snapshot: What does the future hold for narcolepsy treatment?

node leader

Everyone with narcolepsy knows that, as things stand, there is no cure for the condition.  Instead, we rely on medication to control the symptoms, though for many people those drugs do not work well enough or have adverse side-effects.  So what does the future hold?  Will there be new and more effective treatments?  What are scientists around the world working on to help us?

One way to survey the research that is being undertaken is to look at applications for patents that have been published and which describe developments in the treatment of narcolepsy.  Often, what is written in patents is unproven and speculative, but nonetheless patent publications can give an overview of what is going on.

A review of patent publications from the last year or so has revealed the wide range of research into narcolepsy that is going on around the world, and the diverse approaches that scientists are taking to find ways of improving the lives of people with narcolepsy.

Sodium oxybate (Xyrem) is widely regarded as one of the most effective medications for narcolepsy, particularly for the treatment of cataplexy.  A company called Concert Pharmaceuticals, based in Massachussets, USA, is working on slightly modified versions of sodium oxybate that address a major shortcoming of that drug, namely the fact that it has a very short half-life in the body, with the result that patients who take a dose immediately before going to sleep must wake in order to take a second dose only a few hours later.  Concert's International Patent Application WO2014/031840 describes sodium oxybate-type molecules in which some of the hydrogen atoms are replaced by deuterium, the naturally occurring but rare isotope of hydrogen.  This is an approach that has been proposed in relation to other drugs, based on the fact that the deuterium forms stronger chemical bonds with carbon atoms than normal hydrogen does.  As a result, so it is believed, the drug molecules are broken down less quickly in the body, and so the duration of action is increased.

The major pharmaceutical company Novartis, based in Switzerland, has also published patent applications relating to possible treatments for narcolepsy.  International Patent Application WO2014/111751 is based on the suggestion that certain drug compounds, previously found to bind to a particular type of receptor in the body, may be useful in the treatment of narcolepsy.  The application contains some data that shows a reduction in narcoleptic episodes in mice genetically modified so that they do not produce orexin, the absence of which is believed to be the cause of narcolepsy in humans.

Prof Emmanuel Mignot of Stanford University in California is acknowledged as one of the world's leading narcolepsy researchers.  Prof Mignot is one of the inventors named on International Patent Application WO2014/165866, which concerns immune-based methods of diagnosis of narcolepsy.  These methods are to be potential replacements for current methods of diagnosis including invasive measurements of hypocretin in cerebrospinal fluid.  For patients with only partial loss of hypocretin-producing cells, or very slowly progressive narcolepsy, the methods may enable early diagnosis and possible treatments that would prevent complete loss of those cells.

Another investigation into the diagnosis of narcolepsy is described in International Patent Application WO2014/180974.  This relates to methods involving the detection of “volatile organic compounds” in the odour of a sample taken from a person suspected of having narcolepsy.  Ways in which the odour can be detected include so-called “electronic noses”, but the application also mentions that detection can be carried out by an appropriately trained dog.  Patents can only be granted if the invention described is sufficiently different to everything previously known.  The Patent Office carries out a search for earlier documents that it thinks are relevant to the patentability of the invention, and a list of those documents is published with the application.  In this case, one of the listed documents is an edition of Narcolepy UK's own Catnap newsletter, which carries a report of the use of medical detection dogs to diagnose narcolepsy.

An issue of major concern to the narcolepsy community in recent years has been the link between the H1N1 swine flu vaccination campaign and an upsurge in the number of reported cases of narcolepsy.  In particular, a link has been established between narcolepsy and the use of an adjuvanted H1N1 vaccine marketed under the name Pandemrix.  Another patent application from Novartis, US2014/0335116, proposes a form of vaccine that is said to reduce the risk of inducing narcolepsy.

It is now generally accepted that narcolepsy is caused by the loss of cells (neurons) in the brain that produce hypocretin/orexin.  As things stand, the loss of those cells is irreversible and so narcolepsy is a lifelong condition.  If the missing cells could somehow be regenerated, a cure for narcolepsy could become possible.  A patent application filed by a research group at the University of Tokyo, US2014/0349964, describes methods for producing orexin neurons from stem cells.  The application describes how the number of orexin neurons present in the brains of mice were increased, and suggests that the methods it discloses might contribute to the regeneration of lost orexin neurons in people with narcolepsy.

It has to be remembered that patent applications are necessarily filed when research is still at an early stage, and much of what is written in them is speculative and untested.  Unlike papers published in the scientific literature, patents are not peer-reviewed, and much of the research that they describe ultimately fails for one reason or another.  Nonetheless, the fact that the six different patents applications described above were all published within a recent window of one year or so illustrates that research into narcolepsy and possible treatments is underway in both academia and industry in numerous locations around the world.