Clinical trials are aimed at older people who have sleep problems but no cognitive problems
Researchers at the University of Washington School of Medicine in St. Louis are conducting a Phase 2 clinical trial to study whether drugs can be used to treat sleep disorders in the elderly to reduce early signs of Alzheimer’s disease. It has started.
The character of Sitcom’s grandpa on TV, who always seems to fall asleep at unfortunate moments, is very common and almost cliché. However, naps and uncoordinated sleep at night are not part of normal aging. Sleep disorders can be an early sign of a neurodegenerative condition and may be treatable.
Researchers at the University of Washington School of Medicine in St. Louis are conducting a Phase 2 clinical trial to study whether drugs can be used to treat sleep disorders in the elderly to reduce early signs of Alzheimer’s disease. It has started. Positive results indicate a new approach to delaying or preventing the onset of Alzheimer’s disease. The trial is supported by a $ 7.9 million grant from the Good Ventures Foundation, a charitable foundation whose mission is to support the prosperity of humankind.
Brendan Lucey, an associate professor of neurology and director of the Center for Sleep Medicine at the University of Washington, said: “Chronic sleep deprivation can be at risk for Alzheimer’s disease. The main goal of our study is to treat sleep disorders before people show signs of cognitive impairment. It’s about finding out if you can slow down or stop the progression of Alzheimer’s disease. “
Alzheimer’s disease progresses slowly for over 20 years. First, the protein amyloid beta begins to accumulate in the senile spots of the brain. Next, a second brain protein known as tau begins to collect in toxic tangles. Immediately after the entanglement becomes detectable, people begin to experience memory loss and confusion. Lucy and his colleagues have shown that sleep deprivation is associated with high levels of both amyloid and tau in the brain.
Lucy wants to determine if a sleeping pill known as suvorexant, already approved by the Food and Drug Administration (FDA) for the treatment of insomnia, can intervene to slow or slow the accumulation of amyloid in the brain. I think. Suvorexant comes from a family of drugs that suppress a protein called orexin that stimulates the brain to wake you up from sleep. Dr. David M. Holtzmann, Ph.D., Barbara Burton and a prominent professor of Ruben M. Morris III Neurology have shown that another member of this drug class reduces amyloid plaques in mice.
“Suvorexant has been on the market since 2014, so we know it’s safe and tolerable,” Lucy said. “We plan to use the highest dose approved by the FDA in our study.”
As part of this study, Lucy and colleagues recruited 200 people over the age of 65 who had difficulty sleeping and had no cognitive impairment and took suvorexant every night for two years before bedtime. Potential participants do not need to have a diagnosed sleep state. Researchers use wrist-worn accelerometers to track arm movements to estimate sleep length and quality for each participant. Each participant will undergo a brain scan of amyloid plaques again at the beginning of the study and two years later. They are randomly assigned to receive medicine or placebo.
Researchers expect that it will depend on how participants respond to experimental treatment. To better understand the roots of these differences, collaborator Dr. Douglas Bullbaker and colleagues, assistant professors of biomedical engineering at Purdue University, collaborated with participants on blood, cerebrospinal fluid, and stool. Samples are collected and analyzed for differences in gene expression, at the protein level, and the gut flora between responders and non-responders. In addition, Blue Baker will lead another study using mathematical modeling to investigate the differences in response between cell lines and animals to suvorexant. Brubaker’s team translates the results of the model into humans to better understand the role of orexin signaling in the development of Alzheimer’s disease.
This study was not designed to determine whether improving sleep prevents or delays cognitive decline. People with amyloid plaques in the brain but no cognitive symptoms are considered to be in the early stages of Alzheimer’s disease, if not decades after the onset of thinking problems. No cognitive benefit is seen in just two years.
However, researchers may find that amyloid in the brain stops increasing and ideally begins to decrease. If so, it provides evidence that it can stop the seemingly relentless progression of Alzheimer’s disease and provides a strong reason to start Phase 3 clinical trials to look for cognitive benefits of improving sleep. Lucy said.
“There may be quite a few options on the market within a few years, as several other drugs in the same class as suvorexant are currently in clinical trials,” Lucy said. “If we can show that suvorexant alters amyloid accumulation in the brain, we can move on to Phase 3 studies very quickly to see if this approach can delay or prevent dementia.”
For more information on joining, please call 314-273-6102 or email us at luceylab@wustl.edu.
