Caffeine May Help Treat Parkinson's Disease

 Caffeine has previously been linked to a lower risk of developing Parkinson's disease, but now new research says the ubiquitous stimulant may also help treat disease symptoms.

In a small study of 61 people with Parkinson's disease, Canadian researchers found that giving the caffeine equivalent of about three cups of coffee per day improved motor symptoms, such as slow movement and stiffness. Interestingly, caffeine didn't significantly improve daytime sleepiness, a common symptom in Parkinson's disease.
"Caffeine treats Parkinson's disease," said the study's lead author, Dr. Ronald Postuma, an associate professor in the department of neurology at McGill University in Montreal.
"There was a modest effect on sleepiness that didn't reach statistical significance, but I think it was clear that it helps patients," he said. "Where we saw the most potential benefit from caffeine was on motor aspects and symptoms. People felt better and were more energetic. You could see on the exam that they were better."
Parkinson's disease is a degenerative disorder that causes shaking, stiffness, slow movements and difficulty with balance. More than one million Americans have Parkinson's disease, and more than 50,000 people are diagnosed with the disease each year, according to the National Parkinson Foundation.
In the current study, published in the Aug. 1 online edition of the journal Neurology, half of the group of Parkinson's patients was randomly assigned to receive caffeine treatment, while the other half received an inactive placebo.
To be included in the study, the volunteers had to consume less than 200 milligrams (mg) of caffeine daily -- about two cups of coffee -- and they couldn't have any heart rhythm problems, uncontrolled high blood pressure, or an active ulcer.
For the first three weeks of the study, those receiving caffeine were given 100 mg of caffeine twice daily -- once when they got up and again at lunchtime.
During the second three weeks, the dose was increased to 200 mg twice daily.
Using a test called the Epworth Sleepiness Scale score, the researchers found that while there was a reduction in this score for those treated with caffeine, indicating less daytime sleepiness, that decrease didn't reach statistical significance. Still, Postuma said he believed that caffeine did help improve the level of daytime sleepiness, and that with a bigger study group, a benefit would likely become clearer.
Motor symptoms were judged using the Unified Parkinson's Disease Rating Scale score. There was a modest overall improvement of 5 points in this score.
In addition, there were improvements in the speed of movement and the amount of stiffness in the treatment group versus the placebo group.
"[This study] is important even though it failed to reveal a benefit for caffeine in improving sleepiness in Parkinson's disease. Interestingly, it did reveal a clinically significant potential motor benefit," said Dr. Michael Okun, national medical director of the National Parkinson Foundation. "It will be interesting to see if these findings hold up, and caffeine becomes a treatment approach in Parkinson disease," he added.
Postuma said the mechanism behind coffee's effect on Parkinson's symptoms isn't yet known, but it's believed to block receptors of a substance called A2A adenosine that may play a role in some Parkinson's symptoms. Two new drugs that block A2A adenosine receptors and work in a very similar manner to caffeine are currently in development, he said.
"Their results are almost the same as what we're getting. They may be making and selling expensive caffeine," Postuma said.
"One interesting aspect about the actions of caffeine in Parkinson's disease is that they are thought to be mediated through blocking the A2A adenosine brain receptor. There are several drugs in Parkinson's trials that have similar mechanisms of action, and it would be interesting to perform head-to-head trials comparing caffeine to these drugs," Okun said.
Postuma would like to conduct larger trials on caffeine to see if the effects of the stimulant wear off over time.
The good news, he said, is that caffeine is "incredibly safe and well-tolerated."
So, "if you've been avoiding caffeine because you think it's bad, you can stop. If you're sleepy during the day, you can try it," Postuma said. People with heart rhythm problems, uncontrolled high blood pressure or active ulcers should talk with their doctors about whether they should have caffeine in their diet, however.
Home-brewed coffee tends to have less caffeine than what you get at a coffee shop, Postuma noted. Most people shouldn't go over 400 mg to 500 mg a day (about four to five cups), he advised. And, if you don't want caffeine to interrupt your sleep, try to have your last cup of coffee with lunch.

A number of studies have suggested caffeine has the potential to slow Parkinson's disease. Now, researchers have built on these findings, creating caffeine-based compounds that could halt the protein clumping associated with Parkinson's development.

Researchers have developed caffeine-based compounds that show promise for slowing the progression of Parkinson's disease.

Parkinson's disease is a progressive neurological disorder estimated to affect almost 1 million people in the United States.
Signs and symptoms of Parkinson's include tremors - particularly in the hand or fingers - slowed movement, muscle rigidity, speech problems, and impaired balance and coordination.
While the precise causes of Parkinson's remain unclear, there is mounting evidence that a protein called alpha-synuclein (a-synuclein) plays a role.
Studies have shown that in the brains of Parkinson's patients, a-synuclein misfolds to form protein clumps called Lewy bodies, which accumulate in and destroy dopamine-producing cells of the substantia nigra - the brain region involved in movement.
The resulting reduction in dopamine - a neurotransmitter that helps regulate movement - leads to the impaired motor control characteristic of Parkinson's.
As such, researchers have been investigating ways to block a-synuclein accumulation as a strategy to prevent Parkinson's or slow its progression.
In the new study, co-author Jeremy Lee, of the University of Saskatchewan College of Medicine in Canada, and colleagues reveal the development of two caffeine-based compounds that they say could stop a-synuclein from clumping.

Two 'bifunctional dimers' stopped a-synuclein clump formation

According to Lee, the majority of drug compounds in development for Parkinson's have focused on increasing dopamine production of surviving nerve cells, "but this is effective only as long as there are still enough cells to do the job," he notes.

Fast facts about Parkinson's

• Around 60,000 Americans are diagnosed with Parkinson's each year
• Men are 1 ½ times more likely to develop Parkinson's than women
• More than 10 million people across the globe are living with Parkinson's.

Learn more about Parkinson's

For their study - published in the journal ACS Chemical Neuroscience - Lee and team took a different approach; they set out to identify ways to protect dopamine-producing cells by halting the misfolding of a-synuclein.
Previous research has identified caffeine - a central nervous system stimulant present in coffee, tea, and cola - as having a protective effect against Parkinson's disease.
With this in mind, the team used a "caffeine scaffold" to create eight new compounds called "bifunctional dimers," which are molecules that connect two different substances that affect dopamine-producing cells.
Alongside caffeine, other compounds tested included nicotine, metformin (a drug used to treat diabetes), and aminoindan (an investigative drug similar to the Parkinson's drug rasagiline).
The team applied the dimers to a yeast model of Parkinson's disease, which is a yeast cell line that expresses a-synuclein-green fluorescent protein (AS-GFP).
From this, the researchers identified two caffeine-based compounds - referred to as C8-6-I and C8-6-N - that bind to a-synuclein and stop the protein misfolding and forming clumps.
At present, there is no cure for Parkinson's, only medications that can help patients manage symptoms of the disease. According to the authors, these new findings could pave the way to much-needed strategies to prevent or slow the disease.

"Our results suggest these novel bifunctional dimers show promise in preventing the progression of Parkinson's disease."

Jeremy Lee

Lee and colleagues now plan to test their novel compounds in mouse models of Parkinson's.
Learn how a new protein test could enable early Parkinson's diagnosis.

Written by Honor Whiteman

 

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. Classically, PD is considered to be a motor system disease and its diagnosis is based on the presence of a set of cardinal motor signs (rigidity, bradykinesia, rest tremor) that are consequence of a pronounced death of dopaminergic neurons in the substantia nigra pars compacta. Nowadays there is considerable evidence showing that non-dopaminergic degeneration also occurs in other brain areas which seems to be responsible for the deficits in olfactory, emotional and memory functions that precede the classical motor symptoms in PD. The present review attempts to examine results reported in epidemiological, clinical and animal studies to provide a comprehensive picture of the antiparkinsonian potential of caffeine. Convergent epidemiological and pre-clinical data suggest that caffeine may confer neuroprotection against the underlying dopaminergic neuron degeneration, and influence the onset and progression of PD. The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. Finally, recent experimental findings have indicated the potential of caffeine in the management of non-motor symptoms of PD, which do not improve with the current dopaminergic drugs. Altogether, the studies reviewed provide strong evidence that caffeine may represent a promising therapeutic tool in PD, thus being the first compound to restore both motor and non-motor early symptoms of PD together with its neuroprotective potential.