“We identified possible drug targets that we believe may silence serotonin neurons and ease LID in PD.”
Tomas Björklund, Ph.D., Lund University, Sweden
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Solving PD Side Effects: Dr. Björklund Tests New Technology to Ease Dyskinesia in Parkinson's
Are you one of the many people who experience side effects from Parkinson’s disease (PD) medications? Among common side effects are the involuntary twisting and writhing movements called levodopa-induced dyskinesia (LID) that often accompany long-term treatment with carbidopa/levodopa (Sinemet®). Luckily, Tomas Björklund, Ph.D., of Lund University in Sweden, a scientist funded by the Parkinson’s Disease Foundation (PDF), is seeking solutions. In 2013, he was awarded a two-year PDF research grant, which he used to explore cutting-edge technology to help us understand and ease dyskinesia in PD.
Q. Why did you choose to study LID in Parkinson's?
For me, there are two major reasons. The first is to help people with PD. Since we cannot prevent or cure PD, we rely on levodopa as our best treatment. While it can improve quality of life dramatically, it also has flaws. If we could reduce or prevent LID, we could have a real impact on quality of life for many people. This is a strong driving force behind our research. The second reason is to understand the brain and how it adapts to new situations, including changes caused by Parkinson’s. Such knowledge may help us understand how Parkinson’s develops.
Q. Can you summarize your research?
To understand the brain changes behind dyskinesia, we looked at three types of brain cells: dopamine neurons (the kind lost in PD), acetylcholine neurons and serotonin neurons. There are many challenges to studying brain cells, but two new technologies have helped us to overcome them. The first was the development of an animal model: rats with PD symptoms that are very similar to humans. The second was the development of chemogenetics, which allowed us to use designer drugs/chemicals to turn genetically-modified brain cells “on” or “off” like a light switch. It took us nearly a year to make the technology work, but when it did, we were able to study — more closely than ever before — brain cells in a rat model of PD. We studied the effects of the technology both in rats that received levodopa and in rats that received cell replacement, to understand LID in Parkinson’s.
Q. What did you learn about LID?
We discovered information about how the brain works to cause dyskinesia. Our studies showed that LID is caused in part by an imbalance in two types of brain cells — dopamine and acetylcholine neurons. We also found that a third type of brain cell — serotonin neurons — contribute to this imbalance. Lastly, we identified possible drug targets that we believe may silence serotonin neurons and ease LID in PD.
Q. What is your plan for advancing this research?
The next step is to move this research closer to the clinic. Making discoveries in animals is an important first step in research, but turning that knowledge into drugs that can help people is a far more daunting task. The good news is that there are already drugs similar to the ones we have identified in development. But right now, they are being tested for diseases other than PD. Our team has begun discussions with the pharmaceutical industry about the possibility of testing the drugs in PD. A second goal is to develop a “designer drug” technology, similar to the one used in rats, for people. This is not an easy task, but we think that we are on the right track.
Q. Is there anything else you'd like readers to know about this work?
First, I would like to direct a big thank-you to all the people who have supported PDF and thereby, indirectly, our work. It is easy to think that a small contribution isn’t that important, but it is! The sum of this support can make all the difference for enabling a radically new idea to be tested. In my case as a young group leader, it was very tough to get support for my high-risk projects, but the PDF grant made it possible. I hope that PDF can continue to provide this crucial support to others in the future.