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."
Decreases in blood flow were more significant in subjects who had higher blood levels of the investigational drug. More study will be required to learn whether even higher doses might have a bigger influence on brain activity, Black says. It also will be important, he adds, to determine whether the decreased blood flow seen in the MRI scans will ease clinical symptoms of Parkinson's disease, such as tremors, weakness, stiffness and difficulty walking.
But it is clear the drug is influencing brain function, he says. Even if this drug does not have a big impact, the method his team used to study the drug could influence future pharmaceutical research.
"This could shorten the time it takes to get medications to market because you don't need as many patients or as muc
|Contact: Jim Dryden|
Washington University School of Medicine