Meeting Explores Regulatory Requirements for Parkinson's MCI
Most people with Parkinson's disease eventually develop dementia. Similar to Alzheimer's disease, PD dementia begins with subtle deficits in cognition that progress to symptoms recognizable as mild cognitive impairment (MCI). There are no validated diagnostic criteria or outcome measures for PD-MCI and no accepted treatments or approved paths to developing them. In general, when there is no formal indication for a condition, drug developers see little point in investing in drug development for it. Against this backdrop, the Michael J. Fox Foundation convened opinion leaders to discuss what might be the right regulatory requirements for this condition. The U.S. Food and Drug Administration was represented, and FDA scientists indicated that they would be willing to provide an indication of mild cognitive impairment in PD.
Held 18 April 2013 in Bethesda, Maryland, the meeting also drew representatives from academia, industry, and research and development organizations, including the Movement Disorders Society, the National Institute for Neurological Disorders and Stroke, the Parkinson’s Action Network, the Parkinson’s Progression Markers Initiative, and the Coalition Against Major Diseases. The discussion revolved around diagnosis, outcome measures, and the design of cognitive impairment trials for PD-MCI.
Besides expressing their interest in establishing PD-MCI as a therapeutic indication, FDA leaders suggested that this could be pursued without specifying the etiology of the dementia. This is an important consideration for Parkinson's, since unlike Alzheimer's disease, no single underlying pathology for PD-MCI is established. Amyloid plaques, neurofibrillary tangles, and α-synuclein Lewy bodies in thinking areas of the brain all can play a role. With regard to outcome scales, the FDA concluded that co-primary measures—cognitive and functional—would be required to approve drugs for PD-MCI. That is because PD patients, unlike AD patients, do experience subtle functional deficits early in the disease process. The consensus was that for short-term trials, currently used cognitive measures would suffice, but for longer trials, a composite scale akin to the CDR-Sum of Boxes used in AD research would be appropriate. To learn about this meeting in greater depth, download the executive summary prepared by Jamie Eberling and Lona Vincent from MJFF.—Tom Fagan.