Stanford's Emmanuel Mignot, MD, PhD, is well-known for his work on narcolepsy, but he's also a leading researcher in Kleine-Levin Syndrome (KLS), an extremely rare, but devastating, disease that affects primarily male adolescents. There is much mystery surrounding KLS, which affects 1,000 people worldwide and causes periods of excessive sleep (up to 20 hours at a time) and altered (at times bizarre) behavior. There is no known treatment.
This weekend, Mignot and a handful of other academic and clinical investigators are gathering at the KLS Foundation's First International Conference to discuss the disease and latest research. In anticipation of the Bay Area event, which is free and open to the public, I spoke with Mignot about the disorder and his work.
This disease is complex, and its symptoms are unusual. What intrigues you the most about it?
The fact that it is periodic and that people are completely normal [in between] episodes. It is a bit like Dr. Jekyll and Mr. Hyde. Further, the symptoms are fascinating. Many other disorders like depression or bipolar are like this, and there is a feeling we should be able to reverse it for good. It could be a model for understanding these other conditions.
You recently showed that narcolepsy is an autoimmune disease. Is there evidence that KLS could also be one?
It is very possible, although my favorite explanation is rather [that it's] a recurrent type of infection that waxes and wanes, a little bit like herpes.
Can you talk about your current studies on KLS? What exactly are you doing, and have you learned anything from preliminary data?
One of the first things we did was to systematically collect clinical data and biological specimens on a large number of patients. Doing this, we rapidly convinced ourselves that KLS is a real disease entity with a very particular set of symptoms and a classical, predictable evolution. We were also able to demonstrate that one of the key features of KLS is a sort of derealization - an abnormal feeling that the patient experiences during the hypersomnia episodes.
You and other experts are gathering soon to talk about the latest research. Have there been any recent developments that could aid in the diagnosis or treatment of the disorder?
Yes. First, the disease is now better defined and recognized. Second, it seems that almost no treatment works except maybe lithium; [so] often the best course of action is to eliminate other medical problems and to reassure the family by explaining the evolution.
One of the most exciting is the genetic and infectious disease research. We have conducted a genetic scan (a GWAS) in about 250 patients and are going to add 250 more. We hope to find genes prediposing to KLS and from there identify pathways that are involved in the disease... With Charles Chui at UCSF, we are also trying to identify infectious agents such as viruses that could cause the disorder.
Lastly, how does research on this disease, and other rare sleep disorders like narcolepsy, teach us about sleep in general?
When you have a disease that manifests primarily by sleep symptoms, finding the cause can lead you to new mechanisms regulating sleep. For example, when we found that the cause of narcolepsy was a loss of hypocretin/orexin, it indicated that the neurons which produced this chemical are essential to regulate sleep. Now there are multiple drug companies developing hypocretin/orexin blockers to treat insomnia. Similarly for KLS, it is impossible to predict what we will find but likely it will teach us about other periodic disorders, sleep and cognition.
This weekend's conference is being held just south of San Francisco, in Burlingame. Conference organizers are asking those interested in attending to register online.