With long-term use, the gold standard medication for Parkinson’s disease, levodopa, can wear off before it’s time for another dose, causing motor fluctuations called “off” episodes. Complicating treatment is that too much levodopa can cause debilitating side effects such as dyskinesia.

On/off is the focus of The Michael J. Fox Foundation’s Third Thursday Webinar. MJFF CEO Todd Sherer, PhD, talked to MJFF Contributing Editor Dave Iverson for this podcast why levodopa loses its efficacy over time and therapies in development to even out on/off cycles.

“Levodopa is an ingredient used by the brain to make dopamine, says Todd. “And early in the disease the brain contains more of the machinery, the apparatus, the other ingredients that it combines with the levodopa to make what’s needed. So as the disease progresses there’s less and less of those other ingredients to convert to the dopamine. This means for each amount of levodopa you take you really get less bang for the buck.”

Podcast: Causes of Off Episodes

Podcast: Treating Off Episodes

In his next Podcast panellists discuss ways to manage these periods and the importance of therapies in development to prevent or alleviate these times.