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Brain scans show effects of Parkinson's drug

AUDIO: Neuroscientists at Washington University School of Medicine in St. Louis have used a new brain imaging technique to determine that an investigational parkinsons disease drug is affecting blood flow in...

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Neuroscientists using a new brain imaging technique could see an investigational drug for Parkinson's disease get into a patient's brain and affect blood flow in several key structures, an indicator the drug may be effective.

The study represents the first use of the technique in humans called perfusion MRI to test a drug still in development, the lead investigator says. In the future, similar brain scans could speed the development of new drugs and help clinicians learn whether established drugs are working, according to the researchers at Washington University School of Medicine in St. Louis.




Unlike L-Dopa, which works through the brain's dopamine system, SYN115 interacts with the brain's adenosine A2a receptor. That receptor can modify the effects of the neurotransmitters glutamate and dopamine and is thought to be a potential therapeutic target not only for Parkinson's disease but also for insomnia, pain, drug addiction and depression.

"This study is important because it demonstrates this may be a useful approach for studying investigational drugs," says lead investigator Kevin J. Black, MD. "We were able to determine both that the drug gets into the brain to exert its effects and that it has a larger effect at a higher dose."


Although PET scans can measure many of the same things, a large number of medical centers don't have PET scanners, and depending how it's done, PET may cost more, Black explains. The previous method of measuring blood flow with functional MRI is called BOLD scanning (Blood Oxygen Level Dependent).

"That's a wonderful technique for watching someone's brain respond to a question or a task or to compare blood flow changes over short periods of time," he says. "But it's not very helpful in determining the effects of drugs that might not influence the brain for 30 minutes or an hour. The ASL method works much better at comparing brain activity over that longer time period."

SYN115 probably is not a candidate to replace L-Dopa, Black says, but if used with L-Dopa, he believes it may boost that drug's therapeutic benefit and reduce its side effects. His team tested 21 Parkinson's patients, comparing ASL functional MRI scans among patients who took only L-Dopa and those who took L-Dopa combined with either 20 milligrams or 60 milligrams of SYN115. Patients who received SYN115 experienced decreased blood flow in specific brain structures, with the biggest decreases occurring in the thalamus.

"The nerve cells that send signals to the thalamus are mostly inhibitory in nature," Black says. "So we believe these decreases represent the brain taking its foot off of the brake pedal. The more drug in the system, the less 'braking' influence there is on the thalamus, which would then allow the thalamus to send positive signals to the brain's cortex, where movements are initiated."



"This could shorten the time it takes to get medications to market because you don't need as many patients or as much time to determine whether a drug has an effect in the brain," he says. "This imaging technique could make it possible to significantly shorten the time from drug discovery to the launch of large, clinical studies to learn whether it truly is effective."

And the technique has implications beyond Parkinson's disease.

"One example might be depression," Black says. "Antidepressant drugs work for some people and not for others. The drugs exert many effects within the first two hours, but often they don't begin to relieve depression symptoms for a month or more. Theoretically, this imaging test could determine within hours whether we're going to help patients, rather than waiting weeks to see if the drug is alleviating depression."


Contact: Jim Dryden
Washington University School of Medicine

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