Conference Agenda

Optimising interventional trials: how natural history studies and digital technologies can drive innovation

Gráinne Gorman¹, Michelangelo Mancuso²

¹Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom; ²University of Pisa, Italy

Identifying circulating biomarkers to monitor mitochondrial disease severity

Rohit Sharma

Massachusetts General Hospital, United States of America

National mitochondrial disease registry in England: linking genetics with routinely collected healthcare data

Katherine R Schon^1,2, Peter Stilwell³, Jeanette Aston³, Robert D S Pitceathly⁴, Michael G Hanna⁴, Carl Fratter⁵, Rita Horvath¹, Mary Bythell³, Steven A Hardy³, Patrick F Chinnery^1,2

¹Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK; ²Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK; ³National Disease Registration Service, NHS Digital, Leeds, UK; ⁴Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; ⁵NHS Highly Specialised Services for Rare Mitochondrial Disorders – Oxford Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

Status epilepticus in POLG disease

Omar Hikmat^1,2, Karin Naess^3,4, Martin Engvall^3,5, Claus Klingenberg^6,7, Magnhild Rasmussen^8,9,10, Eylert Brodtkorb^11,12, Elsebet Ostergaard¹³, I.F.M de Coo¹⁴, Leticia Pias-Peleteiro¹⁵, Pirjo Isohanni^16,17, Johanna Uusimaa^18,19, Kari Majamaa^20,21, Mikko Kärppä^20,21, Juan Dario Ortigoza-Escobar^22,23, Trine Tangeraas^24,25, Siren Berland²⁶, Rita Horvath²⁷, Niklas Darin²⁸, Shamima Rahman^25,29,30, Laurence A. Bindoff^2,31

¹Department of Paediatrics and Adolescent Medicine, Haukeland University Hospital, Norway; ²Department of Clinical Medicine (K1), University of Bergen, Norway; ³Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; ⁴Department of Neuropediatrics, Astrid Lindgren Childrens Hospital, Karolinska University Hospital, Stockholm, Sweden; ⁵Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; ⁶Department of Paediatric and Adolescent Medicine, University Hospital of North Norway, Tromso, Norway; ⁷Paediatric Research Group, Department of Clinical Medicine, UiT- The Arctic University of Norway, Tromso, Norway; ⁸Women and Children's Division, Department of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway and Unit for Congenital and Hereditary Neuromuscular Disorders, Department of Neurology, Oslo University Hospital, Oslo, Norway; ⁹Department of Neurology, Oslo University Hospital, Oslo, Norway; ¹⁰Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; ¹¹Department of Neuroscience and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; ¹²Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway; ¹³Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; ¹⁴Facultiy of Health, Medicine and Life Sciences, Department of Toxicology, , University of Maastricht, Maastricht, The Netherlands; ¹⁵Neurometabolic Disorders Unit, Department of Child Neurology/ Department of Genetics and Molecular Medicine, Sant Joan de Déu Children´s Hospital, Barcelona, Spain; ¹⁶Department of Pediatric Neurology, Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; ¹⁷Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; ¹⁸Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland; ¹⁹Department of Pediatric Neurology, Clinic for Children and Adolescents and Medical Research Center, Oulu University Hospital, Oulu, Finland; ²⁰Research Unit of Clinical Medicine, Neurology, and Medical Research Center Oulu, Oulu University hospital and university of Oulu, Oulu Finland; ²¹Neurocenter , Oulu University Hospital ,Oulu Finland; ²²Movement Disorders Unit, Institut de Recerca Sant Joan de Déu, CIBERER-ISCIII, Barcelona, Spain; ²³European Reference Network for Rare Neurological Diseases (ERN-RND), Barcelona, Spain; ²⁴Norwegian national Unit for Newborn Screening, Division of Pediatric and adolescent Medicine, Oslo University Hospital, Oslo, Norway; ²⁵European Reference Network for Hereditary Metabolic Disorder; ²⁶Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway; ²⁷Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; ²⁸Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden; ²⁹Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK; ³⁰Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; ³¹Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway

Challenging the norm – outcome measure selection for evaluating therapeutic response in patients with Primary Mitochondrial Myopathy after 12 weeks of treatment with REN001, a novel PPARδ agonist.

Lisa Alcock^1,2, Renae J. Stefanetti^2,3, Oliver Russell^2,3, Alisdair P. Blain^2,3, Jane Newman^2,3,4, Naomi J.P. Thomas^2,3,4, Charlotte Warren^2,3, Huizhong Su^2,3, Philip Brown⁵, David Houghton^2,3, Heather Hunter⁵, Helen Tuppen^2,3, Gavin Falkous⁴, Robert W. Taylor^2,3,4, Albert Z. Lim^2,3,4, Yi Shiau Ng^2,3,4, Catherine Feeney^2,3,4, Iwona Skorupinska⁶, Louise Germain⁷, Enrico Bugiardini⁶, Michael G. Hanna⁶, Robert McFarland^2,3,4, Robert D.S. Pitceathly^6,7, Lynn Rochester^1,2,5, Gráinne S. Gorman^2,3,4

¹Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; ²National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre (BRC), Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ³Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; ⁴NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ⁵The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; ⁶Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; ⁷NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK

Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in m.11778G>A MT-ND4 Leber hereditary optic neuropathy patients

Nancy J. Newman¹, Mark L. Moster², Valerio Carelli³, Patrick Yu-Wai-Man⁴, Valerie Biousse¹, Prem S. Subramanian⁵, Catherine Vignal-Clermont⁶, An-Guor Wang⁷, Sean P. Donahue⁸, Bart P. Leroy⁹, Robert C. Sergott², Thomas Klopstock¹⁰, Alfredo A. Sadun¹¹, Gema Rebolleda Fernández¹², Bart K. Chwalisz¹³, Rudrani Banik¹⁴, Magali Taiel¹⁵, José-Alain Sahel¹⁶

¹Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; ²Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; ³IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; ⁴Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; ⁵Sue Anschutz-Rodgers University of Colorado Eye Center, University of Colorado School of Medicine, Aurora, CO, USA; ⁶Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; ⁷Department of Ophthalmology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan; ⁸Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; ⁹Department of Ophthalmology and Center for Medical Genetics, Ghent University Hospital, and Department of Head & Skin, Ghent University, Ghent, Belgium; ¹⁰Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; ¹¹Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; ¹²Department of Ophthalmology, Alcala University, Madrid, Spain; ¹³Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA; ¹⁴Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; ¹⁵GenSight Biologics, Paris, France; ¹⁶Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France

The mitochondrial stress, brain imaging, and epigenetics study (MiSBIE)

Caroline Trumpff¹, Anna S Monzel¹, Catherine Kelly¹, Kris Engelstad¹, Shufang Li¹, Kalpita Karan¹, Gabriel Sturm¹, Jeremy Michelson¹, Mangesh Kurade¹, Vincenzo Lauriola¹, Sophia Tepler¹, Grace Liu¹, Peter Shapiro¹, Robert-Paul Juster², Stephanie Assuras¹, Richard Sloan¹, Michel Thiebaut de Schotten³, Tor Wager⁴, Michio Hirano¹, Martin Picard¹

¹Columbia University Irving Medical Center, United States of America; ²Université de Montréal, Canada; ³Université de Bordeaux, France; ⁴Dartmouth College, Uniter States of America