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Can "caffeitine" treat Parkinson's?

By Jonathan Charlton, The Star Phoenix

Dr. Ed Krol, Associate Professor of Pharmacy in the College of Pharmacy and Nutrition, is a collaborator on this research project with Dr. Jeremy Lee.

University of Saskatchewan professor Jeremy Lee, an expert on proteins, has found a "promising lead" to a drug that could prevent the progression of Parkinson's - the combination of caffeine and nicotine. But it's not as simple as just drowning yourself in coffee and smoking a pack a day. Here's why:

Which protein are we looking at?

It's called alpha-synuclein. When it misfolds in brain cells, additional chunks of the protein are formed, which interfere with the cell's function and eventually kill it. This causes the shakiness, loss of motor control and slow movement associated with Parkinson's. There are different factors that cause this problem, from genetic predisposition to exposure to pesticides.

One of Lee's previous studies has shown crack users are also at higher risk.

How do nicotine and caffeine fit into all this?

"We were intrigued by our results with methamphetamines because that gave us a direct link between misfolding and a drug which binds to alpha-synuclein," Lee said. So they looked through scientific literature for other ideas, and found coffee drinkers and cigarette smokers have shown decreased incidence of Parkinson's. So Lee and his team decided to find out if those drugs were binding to alpha-synuclein.

How does he measure this?

Lee used a technique called nanopore analysis - essentially a microscopic, electric strainer that can determine the structure of individual proteins. He then added a drug and observed what it did. The work was funded by Parkinson Society Saskatchewan.

What did he find?

Nicotine and caffeine do bind to the protein, just like methamphetamines. But instead of corrupting the cell, they protect it and help prevent it from misfolding. It's a "small but distinctive change," Lee said.

What's the catch?

The effects on the protein depend on the amount of nicotine and caffeine used, Lee said. And the drugs have serious side effects - large doses of caffeine can cause heart arrhythmia, and nicotine is extremely toxic. So the two chemicals "are not in themselves particularly useful," Lee said. "Because of the amounts you would need, they would become too toxic."

So - back to the drawing board?

Not so fast. This summer, Lee will work with Ed Krol in the Department of Pharmacy to develop and test "caffeitine," a hybrid drug that would bind to the proteins more tightly and be less toxic. Since caffeine and nicotine bind to different places on the alpha-synuclein, less of each can be used. "You would essentially get an exponential effect," Lee said.

What's the next step?

"I'm pretty excited, this looks like a promising lead," Lee said. But there are still many things that can go wrong, and there's no guarantee caffeitine will actually be useful, even if it does bind. If successful, however, the drug could halt the progression of Parkinson's; this would then be even more useful when combined with tests, currently in development, that detect the disease very early on. "People who were at risk for developing the disease could start taking these drugs," Lee said.