The Parkinson's Progression Markers Initiative (PPMI), a large-scale biomarker study sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF), is expanding to study individuals with a mutation of the GBA (glucosidase beta acid) gene. Participants will include people with or at increased risk to develop Parkinson's disease. Researchers hope that a greater understanding of the biology and clinical features of these participants will lead to therapies benefiting all Parkinson's patients and ultimately provide strategies to prevent disease onset.

"Insights gleaned from volunteers with genetic mutations will help speed research toward new and improved Parkinson's therapies, benefitting the greater Parkinson's community," said Ken Marek, M.D., Principal Investigator of PPMI and president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Conn.

Mutations in the GBA gene can cause Gaucher disease, a disorder where fatty substances accumulate in body cells. First linked to Parkinson's in 2008, these genetic mutations lower levels of an enzyme that helps break down proteins and lipids. In Parkinson's disease (PD) lower levels of this enzyme are associated with aggregation of the protein alpha-synuclein, the hallmark pathology of PD.

Understanding the differences among people with and without PD who carry mutations such as in the GBA gene may help researchers understand what leads to disease onset and progression. In 2014 PPMI expanded to enroll individuals with a mutation of the LRRK2 or SNCA gene, the two targets of greatest interest in Parkinson's drug development.

One key tool missing from the development pipeline is an accurate way to measure progression of Parkinson's disease: a biomarker. Biomarkers would allow researchers to quickly and objectively measure a therapy's ability to slow, halt or reverse the Parkinson's process. PPMI is studying clinical and imaging data and biological samples of people with a genetic mutation to identify biomarkers, ultimately speeding clinical trials. In addition, when a drug targeting LRRK2, SNCA or GBA is ready for clinical testing, PPMI will have assembled a group of people with these mutations who stand ready to participate in studies.

PPMI will enroll 125 people with the GBA mutation and who have Parkinson's and 125 people with the mutation who do not have Parkinson's. These participants will be followed for five years. By collecting data and samples over time from people who have not been diagnosed with the disease but who carry an associated genetic mutation, researchers can test for characteristics that may denote greater risk of disease onset or, conversely, protection from symptoms.

Known genetic mutations currently account for only 5% to 10% of all Parkinson's cases. The vast majority of Parkinson's cases are idiopathic, meaning researchers do not know what causes the disease. However, study of individuals carrying PD-implicated genetic mutations may reveal disease traits that apply to all PD patients. The PPMI genetic cohort will expand understanding of the pathogenesis of both genetic and idiopathic Parkinson's disease.

Launched in 2010, PPMI is a longitudinal clinical study that collects standardized clinical, imaging and biologic data. Now taking place at 33 clinical sites around the world, the study completed initial enrollment of 423 recently diagnosed Parkinson's patients and 196 controls in April 2013. Since then, the study has expanded to include cohorts of individuals at increased risk of developing Parkinson's disease. Risk factors under study include genetics, REM sleep behavior disorder and smell loss. (Enrollment of the smell loss cohort was completed earlier this year.)

"By studying multiple cohorts, we're covering all bases to find and validate these biomarkers," said Todd Sherer, Ph.D., MJFF CEO. "Expanding PPMI to include another genetic cohort allows science to push forward toward better therapies for people living with Parkinson's today and for those who may be at risk in the future."