A sleeping pill to slow Alzheimer’s and addiction?

What does sleep have to do with Alzheimer’s disease, and addiction? We all know how important a good night’s sleep is for us to feel rested and energetic for the day ahead, but evidence is building that sleep is integral to many other brain functions.

While we might feel we’ve had a great night’s sleep, our brain has been beavering away, clearing out the cellular rubbish accumulated during the day’s hard work and pruning back the unneeded synaptic branches created during each and every interaction.

Dr Laura Jacobson heads the Florey’s sleep and cognition laboratory, and is fascinated by the extensive role sleep plays in keeping us healthy, and how disordered sleep may in fact be a contributor, not just a symptom, of many brain diseases, including dementia and post-traumatic stress disorder.

Alzheimer’s and fronto-temporal dementia are characterised by abnormal build-ups of two proteins, amyloid and tau. These clumps of protein then cause brain cells to die.

Laura is particularly interested in two forms of dementia, Alzheimer’s disease and fronto-temporal dementia. Sleep disturbances are one of the earliest symptoms of Alzheimer’s, even before memory problems begin, although the underlying reasons for this are still unknown.

Therefore, reasons Laura, improving sleep in people with Alzheimer’s or fronto-temporal dementia may also improve their memory, mood and cognitive ability. Traditional sleeping pills are unsuitable though, because they can leave you feeling groggy the next day, increase the risk of a nasty fall, as well as actually disrupting memory formation.

Instead, Laura has become interested in the orexin system, which not only controls our sleep-wake cycles, but also plays a major role in our appetite and eating behaviours – which are also commonly affected in patients with dementia.

The orexins are molecules produced in a very specific region of the brain, which then signal to other brain cells and networks in all parts of the brain. Increasing activity in the orexin system reduces sleep, pushing us towards a waking state. Laura says:

“Higher levels of orexin in the fluid surrounding the brain match up with higher levels of clumping tau in the brain. I suspect that these pathological forms of tau, brought on by Alzheimer’s or fronto-temporal dementia, may be causing orexin levels to similarly rise, thereby disrupting patients’ sleep.”

A new drug for insomnia, suvorexant, blocks the orexin system from telling our bodies to wake up. Laura is evaluating whether suvorexant may be useful for people suffering from dementias caused by a build-up of tau, not only to improve their sleep without increasing risk of physical injury, but perhaps by slowing the disease process directly.

Dr Laura Jacobson and Professor Andrew Lawrence

Professor Andrew Lawrence, head of the Florey’s addiction biology laboratory is also interested in suvorexant, for a completely different reason. He has evidence that blocking the orexin system prevents alcoholic rats from relapsing in response to either alcohol-related cues or stressful stimuli after a prolonged period of abstinence. Andrew now has plans to begin an in-patient clinical trial in 2018 with the department of addiction medicine at St Vincents Hospital, in collaboration with Dr Yvonne Bonomo.

“There are only three pharmaceuticals on the market at the moment for alcohol addiction, and none of them work well at a population level,” says Andrew. “When you consider that alcohol hospitalises 430 Australians every day and kills 15 of them, and alcohol use disorder affects 76 million people around the world, we really need a new way of tackling this devastating medical condition.”