![Parkinson’s Disease: More Than a Movement Disorder?](/sites/default/files/styles/featured_xl/public/images/featured/DNA-Lab-Person_3.jpg?itok=0d_JfZoY)
Last July at the Movement Disorders Society (MDS) annual meeting in Dublin, Ireland, scientists debated whether Parkinson’s disease (PD) was rightly defined as purely a movement disorder. More and more, scientists explained, research indicates that Parkinson’s may involve multiple systems in the body beyond the central nervous system, and it may affect these systems before the motor symptoms of the disease set in.
Now the Parkinson’s Progression Markers Initiative (PPMI), The Michael J. Fox Foundation’s landmark study to identify biomarkers of Parkinson’s disease, is expanding to address this evolving understanding of PD head-on. In 2013 the study is launching a pre-motor cohort to shed light on what happens in the body prior to the onset of PD’s motor symptoms.
This new arm of PPMI focuses on three particular volunteer groups that could help scientists detect the presence of Parkinson’s earlier, and develop treatments that more holistically address the disease. The study will evaluate and follow people who don’t have Parkinson’s but may be at increased risk to develop PD, including:
- people with a loss or reduced sense of smell;
- those with rapid eye movement sleep behavior disorder (RBD);
- those with a mutation in the LRRK2 gene (the single greatest genetic contributor to PD known to date).
"If scientists can learn more about the biological processes taking place in people with any of these three conditions, they may be able to define biomarkers at an even earlier stage,” says Ken Marek, MD, principal investigator of PPMI and president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Connecticut. “This type of information could be vital for Parkinson’s drug development, leading to new targets for drugs to attack the disease before it starts.”
Since PD is a complex neurodegenerative disorder with many underlying causes that differ according to the individual, identifying a biomarker requires sophisticated methods of measurement targeted at various aspects of the disease. For this reason, a large-scale undertaking is required to bring scientists together toward reaching this critical goal. PPMI is that effort. Launched just two years ago, PPMI has already become an invaluable resource for the PD research community at large.
PPMI’s open-source research model means that well-characterized biosamples and robust clinical data are available to scientists around the world in real time — providing an immense, unprecedented resource to speed and unify disparate biomarker validation studies and bring therapeutic breakthroughs closer. To date, PPMI data has been downloaded more than 40,000 times by scientists.
In early 2013, PPMI hit an important milestone, as researchers from the University of Pennsylvania published the first ever paper using PPMI data (on impulse control disorders and PD). PPMI investigators made five presentations on different studies associated with PD at the Movement Disorders Society meeting last summer.
“We are already seeing that people with Parkinson’s have different levels of certain proteins in their cerebrospinal fluid (CSF),” says John Trojanowski, MD, PhD, co-director of the Neurodegenerative Disease Research at the University of Pennsylvania. Trojanowski and Les Shaw, PhD, co-lead the PPMI Biomarker Core and were part of a team of PPMI researchers who presented at MDS.
To date, Trojanoskwi, Shaw and team have analyzed the CSF of more than 100 PPMI volunteers, finding that those with PD have lower levels of the proteins tau, alpha-synuclein and beta-amyloid in their CSF. Over the course of the next year, they will aim to further validate these results in a much larger study group.
“The hope is that through PPMI, we’ll eventually be able to establish a test for PD. It could be something that measures hormones in our blood or proteins in CSF and would be an invaluable tool to help us determine whether or not a person has the disease,” Trojanoskwi explains. No such diagnostic test currently exists for Parkinson’s disease.
While the initial cohort’s recruitment period is nearly complete, the new pre-motor cohort, and others being considered for the future, will continue to require the vision and investment of those who sign up to participate.*
Theresa Salzer, 47, of Waynesville, Ohio, is one of those who have already devoted their time, and bodily fluids, to the search for a cure for PD. Diagnosed in March 2012, she has completed several PPMI visits at the University of Cincinnati study site.
Theresa learned that she had Parkinson’s following a visit to a hand specialist to address lingering discomfort in her hand. Prior to a potential surgery, her physician recommended she visit a neurologist, who told her that she likely had PD. She then visited two more neurologists in order to confirm her diagnosis. In some ways, she says, she was lucky that the hand doctor had experience with Parkinson’s, and was able to help get the diagnosis right, and determine what was going on with her body before surgery. Often a Parkinson’s diagnosis can take years, and misdiagnosis is a common reality for many who later learn they have PD. Finding a biomarker could help to definitively diagnose people with the disease, and to do so earlier.
Theresa is hopeful that science will find a cure for PD in her lifetime. But, more than concerning herself with her own health, she worries for her four sons, and the possibility that they could one day develop the disease, too.
“You have to get involved to make a difference,” she says. “I want to be able to say that I was a part of finding a cure for this disease.”
The pre-motor cohort of PPMI is recruiting three specific groups: those with RBD sleep disorder, those with a smell deficit, and those with mutations in the LRRK2 gene. To find out if you might be a candidate, visit michaeljfox.org/PPMI.
*At press time (March 15, 2013), PPMI had not yet completed recruitment.
This first appeared in the Spring 2013 issue of The Fox Focus on Parkinson's. Read the full issue.