Preventing Intestinal Bacteria from Breaking Down Levodopa May Improve PD Symptoms
Christine Olson, PhD, of the University of California, San Francisco, received a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists to study whether reducing an intestinal bacteria that interferes with the absorption of the Parkinson’s disease (PD) medication levodopa may improve PD symptoms.
“Our research could expand our understanding of how gut microbes contribute to Parkinson's disease drug response and progression,” said Dr. Olson. “It could increase understanding of how people with PD respond to treatment. The findings may help clinicians better target treatments tailored to the individual. In addition, we may better be able to explain why people with PD have variable drug responses.”
Parkinson’s symptoms can often be successfully managed with levodopa treatment. However, many people with Parkinson’s have limited treatment success or negative side effects. The reasons for varied reactions to levodopa treatment are unknown.
Recent research highlights that the trillions of bacteria in the human gut can significantly change how treatments like levodopa are absorbed. This also means the microbes in the gut may impact how effective levodopa can be to people with Parkinson’s.
Dr. Olson’s postdoctoral lab found that a common gut bacterium has an enzyme that may lessen levodopa’s effectiveness. Prior work in the lab found that this bacterial enzyme reduced the amount of levodopa absorbed in an animal model. These data suggest that the breakdown of levodopa caused by gut bacteria may reduce drug absorption and treatment effectiveness in people with Parkinson’s. It is possible that variations in people’s gut bacteria contribute to differences in treatment response.
Dr. Olson will evaluate whether antibiotic-induced reductions in gut bacteria lead to improvement in Parkinson’s symptoms. She will also:
- Evaluate control of enzymes in the gut that lead to breakdown of levodopa.
- Test whether a drug that can inhibit levodopa breakdownin the gut affects movement symptoms.
- Test which gut bacteria and which bacterial genes may interfere with levodopa metabolism.
Dr. Olson’s lab also has an ongoing clinical trial where people with Parkinson’s are either treated with a mild antibiotic or a placebo. She will test intestinal microbe samples from participants with PD before and after treatment. This will show which bacteria are changing in response to the antibiotic.
“We will test for the first time whether models of Parkinson’s disease and people with Parkinson’s have improved symptoms after reduction of bacterial levodopa breakdown,” Dr. Olson said.
“This research may lead to novel ways to improve Parkinson’s disease treatment strategy.”
Of her Parkinson’s Foundation grant award, Dr. Olson said, “I am honored to receive this award in support of our Parkinson's disease research. Receiving this award is a vote of confidence for the potential impacts of our work for people with Parkinson's. Additionally, this award will help support my professional development and academic career.”
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