April 22, 2014

Caffeine and Nicotine Together: Powerful One-Two Parkinson's Punch?

According to media reports last week, University of Saskatchewan professor Dr. Jeremy Lee has “discovered” a potential treatment to prevent the progress of Parkinson’s disease. This therapy is no less than a combination of two substances we’ll identify by their technical names: caffeine and nicotine.

We’ve known for a while that smokers and coffee drinkers seem less at risk for PD. Now we learn about the potential of the two common household drugs to work together . . . and the reason why they appear to function especially well in tandem.

The PD literature is full of references to the protein alpha-synuclein. When that protein “misfolds” in brain cells, more and more of the protein accumulates, damaging the cells and short-circuiting their ability to properly communicate with the body. Eventually, symptoms appear – which may include the classic shakiness we associate with Michael J. Fox and other high-profile people with PD.

Lee knew from his earlier studies that amphetamine use and misfolded alpha-synuclein were linked, and that users had higher PD risk. If amphetamines latched on to the protein to cause the misfolding, then caffeine and nicotine must have some different, protective effect. How could he find out what was happening at the cellular level?

A Combo Punch to Prevent Misfolding Proteins
Funded by the Parkinson Society Sasketchawan, Lee used a special microscopic device to observe the activity of individual proteins. When he added nicotine and caffeine to the mix, he observed that both drugs did indeed bind to the alpha-synuclein protein. But instead of disrupting the cellular activity in the protein -- like amphetamines had done – the nicotine and caffeine had a completely different effect, essentially preventing the alpha-synuclein from misfolding – the PD-causing mechanism.

The combination of nicotine and caffeine had much more protective impact on the neurons because the two drugs attached to different parts of the protein structure, multiplying its ability to prevent the misfolding.

To have any useful effect, humans would have to sit around smoking cigarettes and guzzling coffee all day long -- not exactly a good idea. Overdoing caffeine creates its own health problems, including cardiac arrhythmia. The Surgeon General issued the warning about smoking long ago.

Enter the Hybrid, Caffetine
Working with Dr. Ed Krol, Associate Professor of Pharmacy in the College of Pharmacy and Nutrition, Lee created a hybrid called “caffetine,” which binds more tightly to the proteins – enhancing its protective capacity. This new creation is also considerably less toxic that the two drugs they mimic, so humans could take more of it.

There’s a long road ahead before anyone can tout caffetine as a breakthrough for PD prevention. If it proves useful, it could be administered as soon as someone receives a PD diagnosis, and new technologies -- including advances in our understanding of genetics -- are making it possible to make earlier and earlier diagnoses.

Said Lee, “I'm pretty excited, this looks like a promising lead.”

As it turns out, it was a big week for headlines about Parkinson’s and proteins. I wrote about another discovery: how the LRRK2 enzyme affects proteins to retard – maybe even prevent – the progress of the degenerative disease.

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Several months ago, I wrote about pharmacoperones, recently developed drugs that "rescue" misfolded proteins, enabling them to resume their proper function in cells.

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