The Parkinson Progression Marker Initiative: An Emerging Success Story

In an earlier post Biomarker Qualification Consortia: The ADNI Success Story, I discussed the value of biomarker qualification consortia by highlighting the success of the NIH sponsored Alzheimer’s Disease Neuroimaging Initiative (ADNI).  Here, I would like to raise awareness to another biomarker qualification consortium in the field of neurodegenerative medicine: the Michael J. Fox Foundation sponsored Parkinson Progression Marker Initiative (PPMI).

PPMI is a consortium of academic, industrial, and non-profit organizations dedicated to the assessment and qualification of biomarkers of Parkinson’s disease (PD) through the longitudinal monitoring of early PD patients.  In contrast to ADNI, PPMI main sponsor is the Michael J. Fox Foundation: a non-profit organization dedicated to the advancement of PD treatment through scientific research and public awareness.  PPMI has assembled a total of 21 sites in the US and Europe which will recruit and follow 400 early PD patients and 200 age-matched controls volunteers over a 5-year period.  Similarly to ADNI, PPMI has defined a set of standardized protocols for the assessment of clinical (motor assessment, neuropsychiatric, olfaction) end points and imaging (DATScan, MRI, DTI), biochemical (alpha-synuclein, DJ-1, urate), and genetic biomarkers.  In keeping with the non-competitive spirit of the consortium, all data collected by PPMI will be made available to the scientific community through a centralized data repository.  PPMI also intends to facilitate access the biosamples collected from the study participants.

Although PPMI has only been active since June 2010 and not all sites have been active since the study start, the study has already enrolled 50% of the control participants (goal: 200 individuals) and 31% of the PD participants (goal: 400 individuals).

As it is common for studies of this magnitude, PPMI has encountered a few bumps in the road.  Although DATScan was approved by the FDA for US use on January 14^th 2011, this critical imaging biomarker technology has not been available since February 2011 (status may have changed since this information was released).

Thierry Sornasse for Integrated Biomarker Strategy

Prognostic biomarkers, preventive medicine, and the aging population challenge

By 2050, the US Census Bureau estimated that the number of US residents 65 or older will double to reach almost 87 million, representing about 21% of the US population (2010 estimated: 40.2 million, 13%).

In keeping with this aging trend of the US population, the Alzheimer’s Association predicts that, based on current estimates of Alzheimer’s disease (AD) prevalence (5.4 million or 13% of people 65 or older), between 11 and 16 million of individuals will suffer from AD by 2050.  Similarly, the number of individuals suffering from Parkinson’s disease (PD) is also expected to increase dramatically: the incidence of PD increases dramatically in people 50 and older (see Incidence of Parkinson’s Disease: Variation by Age, Gender, and Race/Ethnicity for reference).  Considering these figures, the need for efficacious treatment of AD and PD are urgently needed (as of today, there is no preventive or disease modifying treatment for either AD or PD). 

Treatment of AD and PD is particularly challenging because when an individual starts to present the clinical sign of the disease, a great deal of damage has already be made to critical structures of the brain.  Therefore, most specialists in AD and PD believe that early intervention will be critical to successful therapies in these diseases.  Ideally, individuals at risks will be treated prior to the onset of any clinical sign of the disease in a truly preventive manner. But, how do you identify individuals at risk?  Genetic predispositions that could be detected by genetic tests only represent a minor fraction of the individuals at risk of AD or PD.  New brain imaging biomarkers and possibly cerebro-spinal fluid biomarkers currently under development could turn out to be valid prognostic biomarkers. However, in this new era of healthcare cost control, it is difficult to imagine that such sophisticated and/or complex techniques could be practically deployed to assess all individuals 50 - 60 and older.  Therefore, I would argue that one of the major challenges of addressing the rise of neurodegenerative diseases is to develop low cost and easily deployable screening prognostic biomarkers that could be used as a preliminary step to the more complex definitive prognostic tests.  Already, the PD community (See PARS study) has explored the possibility of using a low cost olfaction test (UPSIT) to screen for individuals at potential risk of PD.  Briefly, in Parkinson disease, the decrease in the sense of smell frequently occurs prior to the onset of motor symptoms.  Although the loss of smell (hyposmia and anosmia) is not specific for PD, identifying individuals with abnormally low sense of smell represents a valid first screen to enrich for individuals at potential risk for PD.

Thierry Sornasse for Integrated Biomarker Strategy