Progressive Supranuclear Palsy Study Group (PSP)
Chair: Günter Höglinger
Progressive supranuclear palsy (PSP) is an adult-onset neurodegenerative disorder with cerebral tau pathology leading to an akinetic-rigid syndrome with ocular motor dysfunction, postural instability, frontal lobe dysfunction and bulbar dysfunction. Its incidence, 1-2 per 100,000, is about 5% of that of Parkinson’s disease and death occurs an average of 7 years after onset.
The diagnostic gold standard is pathologic diagnosis. Clinical diagnosis remains a challenge. The National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) Criteria have been proposed for the clinical diagnosis (Litvan et al., Neurology 1996; 46:922-930). Validation of these criteria in independent sets of patients demonstrated a high positive predictive value, albeit low sensitivity particularly during the early course of the disease. Specifically, the NINDS-SPSP criteria do not account for the recently described variable phenotypic presentations of PSP.
Presently available treatment options are limited to symptomatic interventions with low efficacy. No protective or curative treatment options are available at present. Basic science continues to identify molecular targets and corresponding interventions. Translation into clinical trials to evaluate their safety and efficacy lags behind. The reasons therefor lie partly in the limited repertoire of study designs specific for PSP. For this purpose we need to develop and optimize clinical scores and scales to quantify disease-specific target symptoms, and to identify surrogate markers for disease progression. Acquisition of the natural history data needed for power calculation is particularly challenging in PSP because of its broad clinical spectrum, absence of commonly accepted clinical sub-classification criteria, and geographical fragmentation of clinical research.
The PSP study group also has an active interest in corticobasal degeneration (CBD). New consensus research criteria have recently been published to facilitate studies of CBD (Armstrong, et al. Neurology 2013; 80: 496-503). Like PSP, CBD is a primary four repeat (4R) tauopathy with strong genetic links to the tau gene (MAPT). Because pathological CBD often overlaps with clinical PSP, and vice versa, both disorders are often considered in parallel, particularly in biomarker and imaging studies. As specific tau-directed therapies are developed for PSP, it is predicted that such agents may also be useful to treat CBD, possibly leading to combined clinical trials in both disorders.
Our overall aim is to stimulate research to improve diagnostic and therapeutic options for PSP and CBD. Specifically, we aim to improve the early diagnosis for PSP and CBD, to create clinical research networks, and to facilitate clinical therapeutic trials in PSP and CBD.
Project 1: To provide an evidence-based revision of the diagnostic criteria for PSP.
Project 2: To develop a valid clinical staging system for PSP and CBD.
Project 3: To promote cooperative clinical research into natural history, diagnostic biomarkers, and progression markers of PSP and CBD.
Project 4: To promote clinical trials aiming to cure PSP and CBD.
Adam L. Boxer
Yvette M. Bordelon
Keith A. Josephs
John C. Van Swieten