PRoBaND

Parkinson ’s Repository of Biosamples and Networked Datasets History Hypotheses Overview Linkage to other studies Dr Donald Grosset Consultant Neurologist Institute of Neurological Sciences Glasgow Funded by Parkinson ’s UK

PRoBAND: history

Parkinson ’s UK places call for major biomarker study Joint scientific and clinical consortia form PRoBaND is the clinical consortium to 2 of 3 studies Discovery Award goes to Oxford group Parkinson ’s UK seeks reactivation of PRoBaND PRoBaND funded by Parkinson ’s UK

PRoBaND: overview

 Prospective clinical study of PD patients and relatives  DNA collected and stored  Serum collected and stored

PRoBaND: concepts

Genetic and biomarker diversity explains the varied clinical phenotype of PD Understanding these mechanisms will improve the design and interpretation of basic science and clinical therapeutic studies Large sample sizes are needed to test subsets of PD patients characterised by particular clinical (or genetic, or biomarker) features

PRoBaND: sample size

Patients

Recent onset PD 2000 Diagnosis under 50 240

Gene tests

100 + 1900 – 12 + 228 –

PRoBaND: sample size

Patients

Recent onset PD 2000 Diagnosis under 50 240

Gene tests

100 + 1900 – 12 + 228 – 150 600 750

Siblings

PRoBaND: sample size

Patients

Recent onset PD 2000 Diagnosis under 50 240

Gene tests

100 + 1900 – 12 + 228 – 150 600 750

Siblings

18 90 72

PRoBaND: recruitment of PD cases

35 centres x (average of) 32 cases x 2 years Around 2200 cases (PD diagnosed within last 3 years or <50 years)

Study visits 6-monthly for 3 years (recent onset) Only 0 and 6 months for young onset Blood sample for DNA tests and biomarker analysis Clinical scoring: motor, non-motor, olfactory

Clinical measurements: patients  Clinician scoring  *Past, social and family history  UPDRS - clinician  Cognitive – MoCA, fluency  *Response to medication  Diagnostic evolution • • • • • • • • • • Patient scoring UPDRS – patient *Smell – UPSIT Depression – HADS Sleep – ESS, RBD, PDSS Autonomic – SCOPA QoL – EQ5D, PDQ39 ICDs – QUIP NMS scoring Wearing-off *Once during study

PRoBaND: recruitment of siblings

25 centres x (average of) 16 cases x 2 years Around 800 subjects (sibs of PD cases recruited to main study)

Visit schedule: 0, 36 months Blood sample for DNA tests and biomarker analysis Health questionnaires and clinical examination

PRoBaND biosamples  Blood for DNA (baseline only)  Serum for biomarkers (every 18 months)  CSF, skin NOT part of the PRoBaND protocol  Consent for future contact included  Parkinson’s UK Tissue Bank enrolment

PRoBaND Basic plan for Parkinson gene tests

Recent onset PD LRRK2 GBA Diagnosis under 50 Parkin (PARK 2) PINK-1 (PARK 6)

PRoBaND Basic plan for Parkinson gene tests

Recent onset PD LRRK2 GBA Diagnosis under 50 Parkin (PARK 2) PINK-1 (PARK 6)  Extend to new techniques eg. immunochip analysis

Project linkage: the ‘Networked Datasets’ component of PRoBAND Oxford PD Discovery grant Queens Square PD MRC study (Clinical component) GWAS and young-onset PD gene studies NMS Long (NILS) Study Parkinson ’ s UK Tissue Bank, Imperial Further studies: eg. MRI for diagnosis / progression

Thanks to…

 Study centre principal investigators, PD nurse specialists and teams 

Parkinson ’s UK

 Glasgow BioMedicine  PRoBaND Committee members  National and international collaborators, advisors  DeNDRoN research network