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Coffee gives drug researchers ideas

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(Bloomberg) — For clues to treatments for Parkinson’s and Alzheimer’s disease, scientists are looking at their morning cup of joe.

What they’ve found is that caffeine, the world’s most widely used drug, does more than wake people up. It’s been linked to improvements in memory and appears to protect against the destruction of brain cells.

Emboldened by these findings, some companies have been designing drugs to replicate those benefits. The most advanced research has been in Parkinson’s.

At least one drugmaker, Kyowa Hakko Kirin Co., won Japanese approval last year for such a product and then began U.S. tests. The challenge is to go beyond the buzz of a vanilla latte to achieve a more powerful effect on the brain — without side effects like headaches, irritability and jitters.

“Caffeine has a major benefit for cognition,” said Jiang- Fan Chen, a professor of neurology and pharmacology at the Boston University School of Medicine. “More and more people believe this is a real serious potential benefit that we should explore.”

Caffeine, found naturally in more than 60 plants, enters the brain quickly once consumed. There, it latches onto cells at the same sites that interact with adenosine, a chemical that acts as a braking system on the brain. By blocking those sites and thwarting adenosine, it creates the jolt of clarity that makes coffee one of the world’s most popular beverages.

At least five large studies have shown that consuming more caffeine can help reduce the risk of developing Parkinson’s disease, said Chen, who co-wrote a research review with Fredholm last year. In one rat study, chronic consumption of caffeine prevented the loss of nerve cells.

One study found that people who drank two or more cups of coffee a day had a 40 percent lower risk of developing Parkinson’s.

One study published in Nature Neuroscience this year found that a dose of at least 200 milligrams of caffeine — the amount in about two cups of coffee — enhanced people’s ability to convert short-term memories into long-term ones. A 2007 study found drinking coffee may help mentally healthy women retain word-retrieval skills.

“One reason we need to develop a drug rather than use caffeine, which can be taken so cheaply, is that we need an effect that is larger than that which can be obtained with caffeine, without the side effects,” said Bertil Fredholm, a Swedish researcher who has studied caffeine’s effects for more than 40 years, in a Skype interview.

Using information about the effects of caffeine to create a prescription medicine hasn’t been easy.

Merck & Co., the second-biggest U.S. drugmaker by sales, ended development of such a treatment for Parkinson’s disease last year after late-stage testing suggested it didn’t work. And Japan’s Kyowa had to postpone plans to bring its drug to the U.S. market.

For Parkinson’s, a disease with no cure that progressively impairs movement, body coordination and speech, drug developers are focusing on the way caffeine targets sites in an area deep in the brain called the basal ganglia, which plays a key role in movement. The medicines zero in on molecular targets on those same sites, known as adenosine A2A receptors, and attempt to block them like caffeine does, albeit more effectively.

The goal of drugmakers is to improve movement in Parkinson’s patients who are already taking medication to control tremors and stiffness. Existing treatments become less effective over time, and side effects harder to endure.

Kyowa’s medicine, called Nouriast, has had a long and rocky road to its first regulatory approval. The Tokyo-based company suspended U.S. tests in 2003 because of safety concerns generated by a rat study. Mineral deposits in the rats’ brains weren’t causing any effects such as inflammation, according to Kyowa.

Last year, Japanese regulators cleared it, making the first approval in the world for a so-called adenosine A2A receptor antagonist in Parkinson’s. Sales will probably reach $37.5 million this year, according to Kyowa.

Now the drugmaker is looking west again. Late-stage testing of Nouriast began in November, with plans to enroll about 600 patients in the U.S. and seven other countries. The research will probably be completed in early 2016, Kazuaki Inoue, a spokesman for Kyowa, said by telephone.

Until there is a caffeine-like drug to improve the functioning of the mind, people can drink tea or coffee, or eat foods such as chocolate.

“We should encourage elderly people to continue drinking coffee in terms of prevention and neuro-protection,” said Chen, whose laboratory studies the role of adenosine A2A receptors in disorders ranging from Parkinson’s to drug addiction. The scientist says he drinks one or two cups of coffee a day.

Because each individual responds to caffeine differently, people shouldn’t necessarily stampede to their local Starbucks. Side effects from too much caffeine include rapid heart rate, anxiety, depression, sleep difficulties, nausea and tremors.

–With assistance from Kanoko Matsuyama in Tokyo and Simeon Bennett in Geneva.

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