Presentation is loading. Please wait.

Presentation is loading. Please wait.

Neurological Predictors of Huntington’s Disease

Similar presentations

Presentation on theme: "Neurological Predictors of Huntington’s Disease"— Presentation transcript:

1 Neurological Predictors of Huntington’s Disease
Clinical Professor Peter K Panegyres MD PhD FRACP PREDICT-HD Neurosciences Unit

2 PREDICT-HD Study Intervention model for HD

3 PREDICT-HD: Objectives
Document natural history of premanifest HD Development of Markers Clinical Imaging Outcome measures Preventative Clinical Trials

4 PREDICT-HD N=1013 participants (premanifest) 32 sites International
N=301 negative control > 35 CAG expansion repeats = cases < 36 gene mutation negative = controls 32 sites International Observational Premanifest HD Annual examination

5 PREDICT-HD Median duration in study = 6 years (range 1-10)
75% sample > 3 years data 15% - 2 years <10% - 1 year N=204 gene expanded participants received a motor diagnosis = converters Dropout < 5% per year

6 Premanifest Staging Group
CAG-AGE product [CAP] score = CAPE = [age at entry] x [CAG ] Estimate proximity to HD diagnosis CAPE can be used to estimate 5 year probability of motor diagnosis CAPE < [low]  years  CAPE  368 [medium] yrs > [high] < 7.59 years

7 PREDICT-HD : Statistics
Change over time – controlling for covariates of age, gender, depressed mood, brain scanner field strength Comparison of premanifest and control  LMER (linear mixed effects regression) 39 variables analysed separately Graphical analysis to represent phenotypic characteristics of HD: Motor, cognitive, psychiatric + Biological (imaging) Functional outcomes

8 PREDICT-HD : Results Variables with largest effect sizes
Regional brain volumes TMS [UHDRS], esp bradykinesia and chorea Decline in cognitive performance in every measrue examined, esp symbol digits modalities test Functional variables, every measure esp TFC Psychiatric variables, esp Obsessive compulsive scale Frontal systems behavioural scale executive and apathy scales

9 PREDICT-HD : Results

10 PREDICT-HD : Results Dystonia Stroop FAS SDMT TFC TMS
Six variables significant acceleration of the slope of participants who converted: Dystonia Stroop FAS SDMT TFC TMS

11 PREDICT-HD : Results Estimated effect size for a two-arm Phase II randomised control trial Effect size 20% Required sample for say TMS = 981 Dropout rate 20% Sample required TMS = 1131 CSF space 20% effect = 332 20% dropout = 386

12 PREDICT-HD Plots of key outcome variables for preventative clinical trials

13 Data derived model for disease progression
PREDICT-HD Data derived model for disease progression

14 PREDICT-HD : Conclusions
Longitudinal change in 36 of 39 measures over 10 years of natural observation study Effect sizes suggest a preventative RCT could be designed to detect treatment effects of 30% Significant measures Clinical phenotype HD – motor, cognitive, psychiatric Biological Functional Specific measure a disease state chosen The effects of ageing Real natural history data

15 PREDICT-HD : Conclusions
1300 gene mutation tested individuals followed prospectively through actual motor diagnosis Phenotypic and biological changes decade prior to, and just after, manifestations of disease Biological progression in premanifest HD is Linear for imaging, cognitive and psychiatric Non-linear for motor and functional Motor expression accelerates as the disease manifests over 15 years prior to motor onset Worldwide collaboration Relevant to clinical trials

16 PREDICT-HD : CSF Collection of CSF to analyse Huntingtin protein and other biomarkers as clues to disease progression

17 PREDICT-HD : Thank You Patients and families Huntington’s Study Group
PREDICT Team – Jane Paulsen & colleagues Rachel Zombor, Mark Woodman, Elizabeth Vuletich, Steve Andrews, Maria Tedesco, Carmela Pestell Staff at the Neurosciences Unit

Download ppt "Neurological Predictors of Huntington’s Disease"

Similar presentations

Ads by Google