World-first clinical trial hopes to stop Parkinson's in its tracks

A drug trial under way at Macquarie University in Australia is taking advantage of an early warning sign of Parkinson's in the hope of stopping the disease before it causes permanent damage to patients' brains.

Acting out dreams may seem harmless enough, but it is a little-known early warning sign of the neurodegenerative condition Parkinson's disease.

As it advances, Parkinson's causes symptoms such as tremors in the hands, slow movement, poor balance and coordination, and problems with speech.

More than 10 million people worldwide are currently living with the disease, which is most common in those aged over 60.

About 15 percent of cases are hereditary, and the rest may be associated with environmental factors such as exposure to pesticides or heavy metals. Age is a key risk factor, and men are twice as likely to be diagnosed as women.

While Parkinson's is not considered a fatal condition, it seriously affects patients' quality of life, and increases the risk of life-threatening falls and infections.

Research has identified that inflammation in the brain is a key driver of the disease in the phase before the debilitating motor symptoms begin to appear.

This is known as the prodromal period, and Macquarie University Professor of Cognitive Neurology Simon Lewis says that treatment at this point might be the best opportunity to defeat Parkinson's.

He is currently leading a world-first clinical trial of a drug developed by Sydney biotech company Syntara. Originally intended as a treatment for fatty liver and eye disease, it was found to be effective in reducing inflammation in rats' brains.

The drug is being tested via a six-month randomised control trial, with three-quarters of participants receiving the active compound, and one quarter receiving a placebo.

Supported by a grant from Parkinson's UK, the study is being led by Macquarie University with Oxford University as the second trial site.

Wild dreams are a warning sign

In the prodromal stage, tell-tale symptoms begin to appear that could easily be overlooked, including loss of sense of smell, difficulty in distinguishing between different shades of the same colour, issues with balance, handwriting becoming smaller, but also violent dreams that manifest in the form of punching, kicking or screaming.

Professor Lewis says on the surface, acting out dreams might seem to be innocuous, but it can be a sign of rapid eye movement (REM) sleep behaviour disorder.

"During dream sleep humans have evolved a system in the brain that stops us from moving and acting out our dreams," he says.

"For our ancestors, this represented an important means of self-protection from predators that hunted at night. However, it appears that damage to the brain's neural pathways in the earliest stages of Parkinson's disease causes a breakdown in this mechanism.

"Over a 12-year period, about 75 percent of people with isolated REM sleep behaviour disorder go on to develop either Parkinson's or a related condition called dementia with Lewy bodies.

"Once the motor symptoms of Parkinson's appear, like tremors and trouble walking, there has already been substantial loss of more than 50 percent of the brain's dopamine producing cells.

"If we can successfully treat the neuroinflammation that is driving the disease at the prodromal stage, we could have the chance to 'cure' these conditions before people start losing those brain cells."

"Like the script to a movie"

Former high school teacher John Clowes, 73, has just joined the trial. Both his grandfather and half-brother had Parkinson's, but at the time he did not realise the disease might be hereditary.

The first indication that something was changing was a shift in his dreams about three years ago.

"I was living out my dreams for the first time, and they were very combative," he says. "I was fighting people, and it was almost like the script to a movie.

"I had never remembered my dreams before, but now I could remember them.

"My wife was noticing too, because I was thrashing around in bed and waking her up.

"It might happen once or twice a week and then not again for months."

After learning this could be an early sign of Parkinson's, and that there was a drug trial available, Mr. Clowes decided to volunteer.

He was diagnosed with REM sleep behaviour disorder shortly afterwards, and has just had his first dose of the trial drug.

"If there's a chance that this could work, and it could help other people, that would be excellent," he says.

For more information about the study or Professor Lewis's research, please email the trial coordinator, Karl Aoun.

Provided by Macquarie University