Stanford Research

STANFORD UNIVERSITY KLS RESEARCH PROJECT

Scientific Research Program

A KLS research program has been established at Stanford University under the direction of Dr. Emmanuel Mignot MD, PhD and co-investigator Dr. Isabelle Arnulf. Studies will focus on possible immune, infectious, neurological and genetic bases for the syndrome. The program will use a range of medical and basic research methods, working together with a multidisciplinary team studying hypersomnia and other sleep disorders at Stanford. The research program has begun establishing a comprehensive medical information database about KLS and the first large scale KLS blood sample collection. While the vast majority of cases are sporadic and cases have been reported in all continents, a few very intriguing cases of co-affected family relationships within this rare disease population have been identified. The first investigations will examine HLA and possible other genetic factors predisposing to KLS. This study is part of a larger Stanford study of HLA predisposing genes in various disorders of excessive daytime sleepiness

Objective of the Research Program

Information about KLS is scattered among approximately 100+ published case reports. To obtain a better understanding of the disease, a comprehensive review article is in preparation and a questionnaire has been prepared to accumulate patient data to better characterize KLS symptoms and look for commonalities among patients.A blood sample collection of up to 200 KLS patients and families (with age, sex and ethnic-matched controls) is being established so that various hypotheses about the possible causes of KLS can be readily tested. This blood sample collection will also be a resource available for other investigations and will hopefully foster further research interest in KLS by clinicians and scientists. A consent form has been approved by the Panel for Human Subjects in Medical Research at Stanford which participants will be required to complete to provide samples to the program.

How to Participate in the Research Program

The first step in participating in the program is to contact Stanford University Research Program directly at . Participants will first be asked to complete a questionnaire.

The questionnaire is designed to collect information about:

· Personal and family medical history, including ethnic information

· History of KLS – symptoms, precipitating factors, kinetics of episodes

· Results of treatments tried, and medical and lab tests taken

After completion of the questionnaire, participants (typically the KLS patient and their parents) willing to provide blood samples will be required to complete a consent form allowing Stanford to use the samples and the data obtained from the samples.  Once the form is complete blood sampling kits (with pre-paid FedEx return) will be sent.

Foundation’s Role

In addition to helping fund this research, the KLS Foundation plays an important role in the program by providing contact information on KLS patients and in motivating compliance.

Researcher’s Background

Dr. Mignot is an Associate Professor of Medicine, Stanford Medical School , Professor of Psychiatry and Behavioral Sciences, Director of the Stanford Center for Narcolepsy, and a Howard Hughes Institute investigator, who is very experienced in clinical and basic research in the area of sleep disorders medicine and is internationally recognized as having discovered the cause of narcolepsy. He has received numerous honors, is the co-author of more than 100 original scientific publications, and serves on the editorial board of scientific journals in the field of sleep disorders research.

Research Program FAQ’s

Please use the following link for questions on the Research project:

http://med.stanford.edu/school/Psychiatry/narcolepsy/KLS.html

STANFORD UNIVERSITY KLS RESEARCH PROJECT PROGRESS REPORT:  JUNE 2005

The KLS research program underway at Stanford University is progressing at a very impressive pace.

The KLS Foundation has partnered with sleep experts at the Stanford University Sleep Center to establish a basic and clinical research program on KLS. This project began in the fall of 2004 in the laboratory of Emmanuel Mignot, MD, PhD, under the direction of Isabelle Arnulf, MD, PhD, working with a small support team.

The research program began with a thorough review of nearly 200 cases of KLS reported in the literature and a complete analysis of the symptoms, risk factors and treatment responses of patients. This comprehensive review has been submitted for publication.Two valuable resources for KLS medical research have been established:(1) the first large scale KLS blood sample collection for laboratory investigations(2) a comprehensive questionnaire of KLS patients and parents to create an information database on KLS.

Status of blood sample collection and questionnaire

Compliance has been excellent. To date, a total of 114 patients with KLS who meet the ICSD-2 Revised criteria have taken part in the study by submitting blood samples and completing a detailed questionnaire. In addition to the patients, 164 parents took part in the study, so complete sets of many patients with both parents are available for genetic and other studies. A collection of age, sex and ethnic matched controls of 115 subjects is complete. The patient database also contains families with multiple occurrences of KLS (siblings, father and son, first cousins).

Responses from the questionnaires have been entered in a large confidential Excel database, stored with restricted access at Stanford University. All data entered have been double-checked and cleaned. The questionnaire collected data about personal & family medical history, history of KLS (symptoms, risk factors, kinetics of episodes, many sleep related questions) and results of treatments tried and medical & lab tests taken.

Statistical analysis on KLS vs. controls questionnaire data has begun. Already a higher incident rate in one ethnic group and a correlation with one risk factor have been identified.

Investigations of the blood samples

From the hundreds of blood kits returned, samples of serum, plasma, and buffy coat cells have been prepared, DNA has been extracted and all stored in a blood bank. First studies are designed to look for possible genetic factors predisposing individuals to KLS.

Various autoimmune diseases are tightly linked to a specific human leukocyte antigen (HLA) type. For example, in narcolepsy, over 90% of the patients carry one specific HLA allele.

A first assay of 220 samples of KLS parents and patients has already been typed for a specific HLA allele and the percent positive is not different from that found in the normal population. These samples have been sent to the Stanford University HLA laboratory for full class-II genotyping.

In an additional project, the serum of approximately 100 KLS patients and controls has been prepared for measuring blood protein disease markers. Already, one serum protein, a marker of acute inflammation, has been shown to be twice as high in KLS patients than in controls.

We are also interested in examining a possible viral role in KLS pathology. To maximize the chance of finding viruses or viral markers, blood samples which were collected during a KLS episode or had clear “infectious signs” at an KLS episode onset have been selected for analysis.

Future

In addition to exploring possible hypothesis for the cause of Kleine-Levin Syndrome, these resources will be available for other KLS investigations and will hopefully foster further research interest by clinicians and scientists in the field of sleep medicine.