'Sleep Hormone' Discovery Leads To Novel Melatonin Drug With Potential To Treat Insomnia

Main Category: Sleep / Sleep Disorders / Insomnia
Also Included In: Endocrinology;  Depression
Article Date: 15 Dec 2011 - 0:00 PST

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A team from the Research Institute of the McGill University Health Centre (RI-MUHC) and McGill University has made a major breakthrough by unraveling the inner workings of melatonin, also known as the "sleep hormone." The research, conducted in collaboration with scientists in Italy, reveals the key role played by the melatonin receptor in the brain that promotes deep, restorative sleep. This discovery led the researchers to develop a novel drug called UCM765, which selectively activates this receptor. The results, published in The Journal of Neuroscience, may pave the way for the development of new and promising treatments for insomnia, a common public health problem that affects millions of people worldwide.

"We've spent many years develop medications that act selectively on a single melatonin receptor to specifically promote deep sleep, which we believe is the key to curing insomnia," says Dr. Gabriella Gobbi, a researcher in psychiatry at the RI-MUHC and the study's principal investigator. "Deep sleep has significant restorative effects, as well as the ability to increase memory and boost metabolism, while lowering blood pressure and slowing the heart rate." To date most treatments for insomnia, such as benzodiazepines, have not been selective for deep sleep, and can lead to dependence and cognitive impairment.

The researchers became interested in melatonin because of its effect on cerebral activity, and its involvement in sleep, depression and anxiety. Melatonin is a critical hormone produced by the pineal gland (located in the brain) in the absence of light stimulation. This hormone, present throughout the animal kingdom, is responsible for regulating sleep and circadian rhythms.

The research team discovered that two principal melatonin receptors, known as MT1 and MT2, played opposite roles in sleep regulation. "We discovered that MT1 receptors act on rapid eye movement (REM) sleep and block non-REM sleep, while MT2 receptors favour non-REM sleep, also known as deep sleep," explains Dr. Gobbi, who is also an associate professor of psychiatry in the Faculty of Medicine at McGill. "Specifying the role of MT2 receptors in melatonin represent a major scientific breakthrough that may designate them as a promising novel target for future treatments of insomnia. This discovery also explains the modest hypnotic effect of the over-the-counter melatonin pills, which act on both conflicting receptors."

Using a drug called UCM765, developed in collaboration with a group of chemists, under the leadership of Professor Tarzia in Urbino and Professor Mor in Parma, Italy which selectively binds to the MT2 receptor, the researchers observed an increase in the phases of deep sleep in rats and mice. Most importantly, UCM765 acts in a brain area called the reticular thalamus, which is the main driver of deep sleep. "This new molecule, contrary to traditional treatments for insomnia, increases deep sleep without destroying the "architecture" of sleep. In other words, it increases the duration of deep sleep while keeping the REM sleep episodes the same," says Dr. Gobbi.

"The development of this pharmacology by means of targeting deep sleep receptors to treat insomnia represents a major advancement in our ability to deal with this common health problem that affects people worldwide," concludes Dr. Vassilios Papadopoulos, Director of the Research Institute of the MUHC.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our sleep / sleep disorders / insomnia section for the latest news on this subject. About the study
This paper was co-authored by Rafael Ochoa-Sanchez, Stefano Comai, Francis Rodriguez Bambico and Sergio Dominguez-Lopez, Gabriella Gobbi (Dept. of Psychiatry, McGill University and Research Institute of the MUHC); Baptiste Lacoste, Laurent Descarries (Depts. of Pathology, Cell Biology, Physiology, Université de Montréal); Annalida Bedini, Gilberto Spadoni, Giorgio Tarzia (Institute of Medicinal Chemistry, University of Urbino, Italy); Marco Mor, Silvia Rivara (University of Parma, Italy); Debora Angeloni (Scuola Superiore Sant'Anna, Pisa, Italy), Franco Fraschini (Dept.of Pharmacology, Chemiotherapy and Medical Toxicology, University of Milan, Italy).
This work was supported by grants from the Fonds de la recherche en Santé du Québec (FRSQ), by the Canadian Institutes of Health Research (CIHR), by the Canadian Foundation for Innovation (CFI), MSBi Valorisation, the McGill University Health Centre (MUHC), and the Quebec Ministry of Economic Development, Innovation and Exportation (MDEIE).
McGill University Health Centre Please use one of the following formats to cite this article in your essay, paper or report:

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posted by Ann Jorn, Ph.D. on 15 Dec 2011 at 8:23 am

This breakthrough in understanding deep sleep and the role of the melatonin hormone provides great hope for the chronically sleep deprived chronic pain sufferer. Sleep is not simply disturbed by pain but when sleep does happen restorative sleep is minimal. This is especially true for those that suffer from fibromyalgia.

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Physician Bias Leads To Variations In Cardiac Procedures

Main Category: Heart Disease
Article Date: 13 Dec 2011 - 2:00 PST

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Physician preferences and hospital characteristics influence the type of procedures performed on blockages of the heart, leading to significant variations in rates of bypass, stent or angioplasty procedures, found an article in CMAJ (Canadian Medical Association Journal)..

There is significant variation in the ratio of percutaneous coronary interventions to coronary artery bypass graft surgeries (PCI:CABG ratio). Both procedures are performed to address blockages of coronary arteries. PCI procedures are less invasive than bypass surgery and were initially used to treat single-vessel heart disease. However, PCI is now used more widely for other conditions, including multivessel heart disease and multiple coronary issues. Rates for the procedure have increased in Ontario but there are indications that certain patients with multivessel disease have better long-term outcomes with CABG surgery than with PCI.

Canadian researchers analyzed data for 8972 patients who underwent diagnostic procedures - cardiac catheterizations - to look at heart function and any blockages or abnormalities in function, between April 2006 and March 2007 at 17 hospitals that perform cardiac procedures in Ontario. They wanted to understand the reason for the variations in the PCI:CABG ratio.

Coronary anatomy was the most important factor in PCI procedures being performed rather than CABG surgery but the recommendation for the procedure and the hospital where it was performed were also influential. The researchers found significant variation in the types of procedures offered, mostly among patients with multivessel disease.

"The variation was not primarily the result of differences in patient characteristics or the utilization of primary PCI (i.e., for emergent ST-segment elevation myocardial infarction [MI])," writes Dr. Jack Tu, Institute for Clinical Evaluative Sciences (ICES), with coauthors. "Rather, it appeared to reflect variations in treatment preferences and practice styles of the cardiologists performing the index catheterizations with regard to the management of patients with non-emergent multivessel disease, patients who could potentially be recommended for either PCI or CABG surgery."

"We found that the recommendation of the physician performing the diagnostic catheterization and the treating hospital were strong independent predictors of the mode of revascularization," write the authors.

The authors suggest changes that can lead to more consistency and transparency, such as creating multidisciplinary teams with the interventional cardiologist, a cardiac surgeon and referring physician, if possible. "Although many patients may still prefer PCI because it is less invasive, cardiac surgeons need to be more involved in clinical decision-making when patients are candidates for either PCI or CABG surgery. Patients need to be fully informed about the benefits and risks of all alternative treatment options," they conclude.

In a related commentary , Drs. David Holmes Jr. and Charanjit Rihal of the Mayo Clinic write that, for patients who could be recommended for either PCI or CABG, "the experience and training of the physician performing the angiography plays an important role. For example, an experienced interventional cardiologist trained in procedures to treat chronic total occlusion may recommend PCI, whereas a less experienced interventional cardiologist may favour surgical referral."

They conclude that the decision should be made based on the risks and benefits of all treatment options so that a patient may decide without being influenced by physician bias.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Study Leads To Simpler Therapy For Treating Latent Tuberculosis

Main Category: Tuberculosis
Article Date: 09 Dec 2011 - 2:00 PST

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Research, led by Timothy Sterling, M.D., professor of Medicine at Vanderbilt University Medical Center, has led to an important change in CDC recommendations in the regimen for prevention of the centuries-old scourge, tuberculosis (TB). Sterling's work is published in the Dec. 8 New England Journal of Medicine (NEJM).

On Friday, Dec. 9, The Centers for Disease Control and Prevention (CDC) announced in the Morbidity and Mortality Weekly Report (MMWR) that the new regimen, which takes one-third the time of current therapy, offers an effective treatment option for many patients at high risk for developing TB. Latent TB infections result from exposure to TB, without the contagion and illness caused by the disease itself.

Up to now, the regimen for latent TB infection was daily doses of a drug called isoniazid (INH). A total of 270 daily doses were taken over the course of nine months to eradicate the bacteria, which can lie dormant in the body for years.

The study of 8,000 patients in four countries over 10 years showed that just twelve doses, given once-weekly, of INH combined with another TB drug called rifapentine was as effective. The shorter, weekly combination therapy was safe and effective, but perhaps the most important finding was the new therapy improved compliance by at least 10 percent.

"This is a game changer. Currently less than half of the people who start the current therapy complete it. The new combination would require direct observation, but more people would complete treatment," Sterling said.

The CDC said while cases of active TB are at an all-time low, approximately 4 percent of the U.S. population, or 11 million people, have latent TB. Active TB cases, which can be deadly to patients who have a compromised immune system, still occur in Nashville. To prevent a resurgence of active and infectious disease, the Metro Nashville Public Health Department's Division of TB Elimination works with an average of 700 new cases of latent TB per year.

The Metro Nashville Public Health Department was one of the sites for Sterling's study, which was funded by the Centers for Disease Control and Prevention (CDC). Other Vanderbilt investigators included Amy Kerrigan, MSN, R.N., and Alicia Wright, among others.

Sterling says continued research is important. The new treatment is not an option for all patients, and may not work well in nations where TB incidence is higher. Children under 2 were excluded from the study.

Article adapted by Medical News Today from original press release. Source: Vanderbilt University Medical Center
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