Coffee Fuels Drive for Drugs for Parkinson’s to DementiaKristen Hallam
For clues to treatments for Parkinson’s and Alzheimer’s, 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. 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.
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.
Turning that understanding into a 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.
“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.
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.
“It’s this converging of epidemiology and animal studies on the neuroprotective effect that has excited the field,” he said.
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.
The drugmaker filed an application for Nouriast with U.S. regulators in 2007 and failed to win Food and Drug Administration backing the following year. The agency at the time cited concerns that the drug might not work well enough to be useful to Parkinson’s patients, Kyowa said.
After that, Kyowa focused on developing Nouriast for its home market. 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 3.8 billion yen ($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.
While the approach has been difficult to get right, it remains promising, according to Fredholm, the long-time caffeine researcher who is a professor at the Karolinska Institute in Stockholm.
In fact, Kyowa isn’t alone. Two European drugmakers, Belgium’s UCB SA and Biotie Therapies Oyj of Turku, Finland, are working on an adenosine A2A receptor antagonist for Parkinson’s called tozadenant. The companies plan to start the final stage of human testing in the first half of next year, said Antje Witte, a spokeswoman for UCB.
Others are focusing on different illnesses.
Vernalis Plc of England, for example, has an experimental product that could work for Parkinson’s but instead the company decided to focus on a different disorder of the central nervous system, according to Chief Executive Officer Ian Garland. Test results for the drug, called V81444, are due in the first half, Garland said in a telephone interview.
“We thought there was better potential value in looking at a broader use,” he said. “So it’s in a central nervous system disease, but we’re not saying which one.”
Heptares Therapeutics Ltd., a closely held inventor of compounds that target sites like adenosine receptors, sees promise for similar drugs to help patients with attention deficit hyperactivity disorder or memory problems.
Scientists from the Welwyn Garden City, England-based company published research in 2011 on the structure of the caffeine molecule as it binds to adenosine receptors, information that can serve to design a more effective medicine.
“If you could get a clean and turbo-charged caffeine, it’s probably not going to hurt you and could do you some good if you have ADHD or cognition deficiency,” Heptares Chief Executive Officer Malcolm Weir said in a telephone interview.
Several studies that have collected information from the same people over a long period of time support the theory that consuming caffeine curbs cognitive decline, according to Chen.
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.
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.
“There are individuals who shouldn’t drink any coffee or tea at all, and there are others who can safely take a lot,” said Fredholm, who starts his day with coffee and then switches to tea. “One should simply listen to one’s own body.”