Clinical trial readiness for POLG-related mitochondrial disease and ataxia: a prospective, longitudinal study identifying sensitive and ecologically valid biomarkers
Studying treatments for ultra-rare forms of mitochondrial disease is challenging. Participant pools are small and restricted by rigid inclusion and exclusion criteria. There is often incomplete understanding of genotype–phenotype relationships and natural history to inform trial endpoint development. Tackling these disparities is recognised as a long-standing, complex conundrum. Leveraging value in multi-stakeholder innovative networks is urgently needed. C4TR-POLG will capitalise on existing pockets of world-class excellence in POLG- related mitochondrial disease and ataxia (Newcastle upon Tyne, Tübingen and Bergen) and will explore the appropriateness and scalability of emerging outcome measures and potential barriers to their adoption. C4TR-POLG is a longitudinal study involving two recruitment sites, Newcastle upon Tyne, UK (PI: Dr Ng) and Tübingen, Germany (PI: Prof Schӧls). The target recruitment number is 40 participants and the aims of the project are:
- to exploit instrumented measures of balance and gait using wearable sensors in a controlled setting (clinical research laboratory) repeatedly (3 times in 12 months) in ambulatory patients with POLG-related mitochondrial disease (Dr Alcock and Dr Winfried);
- to confirm the feasibility of monitoring real-world mobility (habitual activity and gait) in patients with POLG-related mitochondrial disease (Dr Alcock and Dr Winfried);
- to compare the changes of clinician-reported, patient-reported measures (Dr Ng, Dr Newman, Prof Gorman and Prof Schӧls) and fluid biomarkers (Prof Hudson and Dr Varhaug) between ambulatory and non-ambulatory patients with POLG-related mitochondrial disease;
- to explore the roles of different fluid biomarkers in predicting and monitoring disease progression of POLG-related mitochondrial disease (Prof Hudson and Dr Varhaug).
This programme of work will build capacity and develop new collaborative ways of working together to generate richer, more relevant data to accelerate global POLG-related research, connectivity, and improved patient care.
Translational and Clinical Research Institute
Dr Yi Shiau Ng, MBChB (Hons), MRCP (Neurology), PhD
Clinical Senior Lecturer and Honorary Consultant Neurologist Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, UK.
Dr Lisa Alcock, BSc (Hons), PGDip, PhD, FHEA
Dr Jane Newman, PhD
Prof Gavin Hudson, BSc (Hons), PhD
Prof Gráinne S Gorman, MB, BCh, BAO (NUI), LRCP&SI (Hons), PhD
Collaborators in University of Tübingen, Germany
Prof Ludger Schӧls, MD
Dr Ilg Winfried, PhD
Collaborators in Haukeland University Hospital, Norway
Dr Kristin N Varhaug, MD, PhD