Two recent papers outline the progression of Parkinson's disease (PD) movement or motor symptoms in distinct study populations. While these findings do not provide an absolute picture of how one person will progress with PD, the results may help researchers design smaller, faster and less expensive clinical trials of new treatments.
Changes in Early Parkinson's and with Dopamine Therapy
The Parkinson's Progression Markers Initiative study, sponsored by The Michael J. Fox Foundation (MJFF), reported on changes in motor symptoms over five years from people who joined the study early in their disease (within two years of diagnosis). The largest change (as measured by the Unified Parkinson's Disease Rating Scale or UPDRS) came in the first year, then symptoms plateaued as people began taking dopamine medication.
Many studies of therapies that aim to slow or stop disease progression recruit people in similar early stage of disease. Understanding what to expect over the first year and as those study participants begin dopamine medication can help drug developers design their trials.
Slower Progression in G2019S LRRK2 Mutation Carriers
Analysis from the LRRK2 Ashkenazi Jewish Consortium -- part of the MJFF-supported LRRK2 Cohort Consortium -- compared progression in people who carry the G2019S mutation in the LRRK2 gene, a leading genetic cause of Parkinson's disease, to progression in people without a known cause of their disease (so-called sporadic PD).
People in the study who carried a G2019S LRRK2 mutation advanced 30 percent more slowly on the UPDRS than people with sporadic PD. The authors from Mount Sinai Beth Israel Medical Center in New York noted, though, that they could not confirm whether those results were from a subgroup with less severe disease bringing down the average or if most G2019S LRRK2 mutation carriers have less aggressive disease.
It is not to say, either, that if you do not carry this genetic mutation you will definitely progress quickly; Parkinson's is a highly variable disease.
The results are already helping companies testing therapies against LRRK2 dysfunction. Carole Ho of Denali Therapeutics, which brought the first LRRK2 drug into clinical trials late last year, told research news website AlzForum, "We are using the new data to design trials to test LRRK2 inhibitors. Knowing the natural course of disease is very important."
PPMI is recruiting people of Ashkenazi Jewish descent with a Parkinson's or Gaucher disease connection. Learn more about the study.