Filling knowledge gaps in the sleep field

By Thomas M. Heffron
Monday, June 4, 2012

In 2009 the ASMF created the Strategic Research Awards grant program to support research that addresses significant knowledge gaps in the field of sleep medicine. The first cycle of the grant program requested proposals to study the effects of gender on the manifestations, diagnosis, treatment or impact of sleep disorders. In 2010 and 2011, the focus shifted to projects promising novel therapeutic and diagnostic tools or improvements in quality of healthcare delivery in sleep medicine.

Jan Polak MD, PhD, a post-doctoral fellow at Johns Hopkins University in Baltimore, Md., received one of two ASMF Strategic Research Awards in 2011 for the proposal, “Effects of endothelin-1 antagonists on metabolic dysfunction induced by intermittent hypoxia in a mouse model.” According to Dr. Polak’s proposal, the study will build on a decade of research demonstrating that obstructive sleep apnea (OSA) is independently associated with insulin resistance, glucose intolerance and type 2 diabetes mellitus. In particular, several studies suggest that the metabolic effects of OSA are mediated, in part, by intermittent hypoxemia.

Dr. Polak’s preliminary data suggest that circulating endothelin-1 (ET-1), a vasoactive peptide released by the endothelium, plays a vital role in the metabolic disturbance associated with intermittent hypoxia. Defining the role of ET-1 in OSA-related impairment in glucose metabolism is the objective of the ASMF-supported study.

Dr. Polak reports that the potential implications of the study are dramatic. It may shed light on the pathophysiological links between OSA and other conditions such as hypertension and cardiovascular disease. Furthermore, the study may open the door for approved ET-1 antagonists to be used as a complementary treatment of metabolic and non-metabolic consequences of OSA.

Marina Hinojosa-Kurtzberg, PhD, a research associate professor at the Biomedical Research & Education Foundation of Southern Arizona in Tucson, received the other 2011 ASMF Strategic Research Award for the proposal, “Effect of prolonging sleep duration on body weight.” Dr. Hinojosa-Kurtzberg’s proposal noted that a knowledge gap exists in our understanding of the mechanisms underlying the relationship between obesity and sleep duration.

Dr. Hinojosa-Kurtzberg proposes that the sleep-promoting cytokine interleukin-6 may have a central role in the complex relationship between sleep and obesity. IL-6 production is elevated by sleep deprivation, and IL-6 gene polymorphisms are associated with obesity in humans. To provide insight for future human trials aimed at modifying sleep duration to achieve weight loss, the ASMF-supported study will use systems biology research to evaluate the opposing influences of IL-6 and the hormones leptin and ghrelin using a mouse model.

The study could have important ramifications for the scientific and medical community’s response to the obesity problem. According to Dr. Hinojosa-Kurtzberg, discovering that pharmacological extension of sleep duration leads to weight loss in mice would provide evidence to support similar research in humans. Ultimately, pharmacogenomics could help personalize therapies aimed at producing weight loss by modifying sleep duration.