Search for risk signature moves into crucial second phase

Parkinson Progression Marker Initiative 2.0, a Michael J Fox Foundation initiative, is ready to roll in a further ambitious effort to identify when and where the disease begins and how it develops in the long period between the onset of neurodegeneration and the emergence of diagnostic motor symptoms.

Our ultimate goal is to slow – even prevent – development of Parkinson’s disease. The opportunity is in the long prodromal phase. And the way that we will gain the understanding needed to guide potentially neuroprotective interventions is through the large-scale, long-term collection of data from people at enhanced risk of developing the condition. 

Such is the task, and such is the promise – as outlined at the virtual AAT-ADPD meeting by Ken Marek (Yale University, New Haven, Connecticut, USA).

PPMI 2.0 will include two thousand people at risk of developing PD over 3-5 years


More people, more measures

Like the initial Parkinson Progression Marker Initiative, which began ten years ago, version 2.0 is a worldwide study covering a comprehensive range of motor and non-motor functions, biosampling, imaging and genetics.

PPMI 2.0 will extend the scope of research by covering more subject-reported outcomes, by including biopsy of the skin (for synuclein) and the microbiome, and through magnetic resonance and non-dopamine PET imaging. As with the first initiative, all data will be freely available to researchers.

Risk assessment is based on hyposmia, REM sleep behavior disorder (RBD), and the presence of rare genetic mutations. Selection of the non-genetic risk factors is based on evidence that they contribute significantly to the likelihood of a person developing PD.

The aim is a roadmap for PD prevention trials, target discovery and validation

The PARS study, for example, found that selecting hyposmic individuals increased the likelihood they would show a deficit on dopamine transporter (DAT) imaging from 8% to 28%.1 And, according to data presented by Professor Marek, a third of people with RBD at baseline can expect to be diagnosed with PD over the next 3-4 years.


Moving up the prodrome pyramid

The new initiative starts with 100,000 participants in the Fox Insight program who will use the on-line platform to judge risk based on a questionnaire and a digital phone app that tests motor and non-motor function.

Fifty thousand with some evidence of risk will progress to stage 2 where there is further assessment (including hyposmia and RBD), but still conducted remotely. Around six thousand will be selected for the clinical stage in which there is face-to-face assessment and DAT imaging.

Based on this, two thousand people will be selected for intensive, clinic-based followed up for five years. And it is in this core group that researchers hope to establish the all-important prodromal biomarker signature.

Recruitment is planned to be completed in 2023, with follow-up to finish by the end of 2028.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


1. Jennings D, et al. Neurology 2014;83:1739-46