A visitor might not realize this was a meeting devoted to people who experience excessive daytime sleepiness. The 2015 Hypersomnia Foundation Conference on Saturday was full of energy, with:

*more than 245 attendees, about twice as many people as last year’s conference

*medical experts from France, Wisconsin and Louisiana — in addition to Emory

*data from several recent clinical trials

*some signs of industry interest in hypersomnia

Hypersomnia is a sleep disorder in which individuals feel frequent or constant sleepiness and need to sleep for long portions of the day (more than 70 hours per week). It is distinct from other sleep disorders such as narcolepsy and sleep apnea, but its prevalence is still unclear. Conventional stimulants such as amphetamine or modafinil often can be used to treat the sleepiness, but some with hypersomnia find these drugs ineffective or hard to tolerate.

Previous research at Emory has shown that many individuals with hypersomnia have a substance in their spinal fluid that acts like a sleeping pill, enhancing the action of the neurotransmitter GABA. The identity of this mysterious substance is unknown, but Emory researchers report that they are close to identifying it. That could give hypersomnia a “molecular handle” similar to what narcolepsy has, with loss of hypocretin-producing neurons.

The terminology is still up in the air — keynote speaker Isabelle Arnulf from Paris said, “The term ‘idiopathic hypersomnia’ does not mean that you are an idiot.” Rather, she said, it means that even specialists can have trouble distinguishing hypersomnia from other sleep disorders, and “idiopathic” signifies that the detailed cause is still under investigation.

Arnulf estimated that idiopathic hypersomnia’s prevalence is less than but roughly comparable to that of narcolepsy, and she reported that in the last year, she and her colleagues had seen 422 patients with the category of narcolepsy, 381 with idiopathic hypersomnia and 178 with Kleine-Levin syndrome. We found this notable: within those categories, there were 231 who had narcolepsy with cataplexy (the sudden collapse that is linked to hypocretin-deficiency) vs 284 in the category of idiopathic hypersomnia with long sleep.

Arnulf warmly described several anecdotes of patients’ difficulty awakening and the absentminded behavior associated with hypersomnia, which she called “a true disabling disease” needing more attention from health authorities.

She described recent studies on an experimental drug, pitolisant: a 2014 Sleep Medicine chart review study in hypersomnia, and a 2013 Lancet Neurology comparison vs modafinil in narcolepsy.

Pitolisant is different from the GABA-targeting drugs studied at Emory because pitolisant enhances histamine release (remember that anti-histamines can make you drowsy). The Sleep Medicine paper says about a third of hypersomnia patients responded to pitolisant and reports some side effects, which Arnulf described as “relatively low” compared to stimulants often used to treat hypersomnia.

Arnulf said she thought pitolisant could become a viable option for people with hypersomnia. Pitolisant is not now commercially available but it has an orphan drug designation from the FDA for narcolepsy.

The conference was structured so that there was a keynote speaker, Arnulf; a main after-lunch speaker, Emory’s Lynn Marie Trotti; and a wrapup from Emory’s David Rye.

Most of what Trotti discussed has been covered in the 2012 initial study on flumazenil in Science Translational Medicine, and in the Emory team’s more recent studies of clarithromycin. Trotti said several options are emerging for hypersomnia when modafinil or other stimulants are unsatisfactory, but each of these options might not become a remedy for a majority of patients.

In between were medical talks from speakers such as David Plante, who outlined the intersection between psychiatry and sleep medicine as it applies to hypersomnia. Plante, from the University of Wisconsin, said that studies of hypersomnia usually exclude people experiencing depression, but the phenomenon of excess sleep and sleepiness in depression needs more study.

Emory GABA signaling experts Amanda Freeman and Andrew Jenkins each gave two education-oriented sessions titled “GABA 101″ and “What’s going on in my head? How do we test your cerebral spinal fluid in the laboratory?”, respectively. The conference schedule also included talks from patient advocates and on employment/education/Social Security disability law, technological aids and service dogs.

Side note: Lab Land attended a presentation by Alanna Wong and colleagues Stephen Maier and Lori Haller Schiller from the Kleine-Levin Syndrome Foundation. Although hypersomnia and KLS share the basic symptom of excessive sleepiness, board members’ descriptions made it seem that there are differences, in that KLS is episodic while hypersomnia is usually constant. Wong described falling asleep on a bathroom floor at her school at age 14, and later spending her entire Outward Bound three day solo in her sleeping bag.

Asked about the possibility of obtaining spinal fluid samples during KLS episodes, Maier said there may be obstacles since KLSers become disoriented during episodes and could be combative. He also said that for some, KLS episodes become less frequent and more predictable as patients reach adulthood.

Wong has reported that she experienced some relief of her sleepiness with flumazenil (she described this on her blog) but its effectiveness diminished in a later episode, she said. Wong’s doctor Nathaniel Watson has reported that the effect of clarithromycin similarly “dissipated over time.”

Final note: some level of industry involvement can be seen in the conference sponsors.

“Gold level”: Arise (clinical study), Flamel Technologies (maker of micropumps)

“Silver level”: Pavilion Pharmacy (flumazenil supplier), Emory WHSC

Two industry-sponsored clinical trials relevant to individuals with hypersomnia were discussed at the conference, but they are in early stages of recruitment/organization: Jazz (JZP-110 for narcolepsy +/- cataplexy), Arise.