Editorial: Mitochondrial medicine special issue

Abstract

This Mitochondrial Medicine special issue of the Journal of Inherited Metabolic Disease includes a mini-symposium of articles based on platform presentations at the 4th International Conference on Mitochondrial Medicine hosted by The Wellcome Trust at Hinxton Hall on the Genome Campus in Cambridge, UK, from 11 to 13 December 2019. The guest editors of this issue include the three organizers of this exciting conference, which brought together critical academic, clinical and corporate stakeholders committed to the development of new treatments for rare mitochondrial disease, as well as patient and family advocacy groups. One hundred and twentyone delegates attended from 21 countries around the world, including physicians and laboratory scientists based in hospitals, universities, and the life sciences industry. Formal feedback confirmed our strong impression that the vibrant atmosphere of the conference was pivotal to forging new strategic partnerships and collaborations, particularly between clinicians and academic experts with a suite of new drug developers working in the pre-clinical and clinical trial space. We believe that nurturing and extending these relationships is pivotal to accelerate the much needed discovery and effective development of new treatments for mitochondrial diseases in the short-to-medium term. This was the fourth of a series of Wellcome Trust Conferences on Mitochondrial Medicine. The first conference in 2013 focused on recent advances in understanding the biology of mitochondrial disorders and how this new knowledge might be harnessed to develop new treatments. At that time, a critically needed step was the development of representative animal models for mitochondrial disease that were becoming feasible based on recent advances in genetics. While some animal models had no phenotype or developed a disease that only loosely resembled the human condition, several showed real promise to help facilitate the pre-clinical development of new medicines. A number of these models were developed and broadly harnessed by the field. At the second Conference in 2016, we began to see pre-clinical treatment effects from repurposed medicines that would subsequently be tested in patients. Throughout this period, the field also witnessed a dramatic advance in diagnostic capabilities, initially through targeted gene panels, then exome sequencing, and eventually genome sequencing. Although not yet providing a comprehensive diagnosis for all patients and families, genomic advances have yielded an extraordinary number of novel mitochondrial disease genes. At the third Conference on Mitochondrial Medicine in 2018, the programme expanded to include several human intervention studies, with early phase trials emerging across the globe, in large part through the establishment of international consortia. By the fourth Conference in December 2019, 102 clinical studies in mitochondrial disease were registered on www.clinicaltrials.gov, 55 of which were testing interventions. Not only is the number of trials increasing, but also the number of distinct therapeutic modalities is growing and includes small molecules, metabolite replacement, gene therapy, and cellular therapy. While there are still no approved medicines for mitochondrial disease by the Food and Drug Administration in the United States, 2019 saw idebenone licensed by the European Medicines Agency for Leber Hereditary Optic Neuropathy and taurine by the Japanese Pharmaceuticals and Medical Devices Agency for Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes Syndrome (MELAS). The remarkable growth of interest and expertise committed to developing new treatments for mitochondrial disease represents extraordinary progress, increasingly matched with significant government and commercial investment. The Conference programme in December 2019 took us one step further, embracing and promoting direct engagement between academic scientists, clinicians, and colleagues from diverse aspects of the life sciences industry—interspersing talks from all three communities with poster and discussion sessions specifically aimed to encourage cross-disciplinary interaction. This issue of JIMD provides a sampling of the gamut of presentations at this meeting, from fundamental research to addressing practical hurdles in drug development, including how to work with regulatory agencies, what is required by industry to move from an early concept to a licensed medicine, and the critical need to develop reliable noninvasive biomarkers of disease progression and other outcome measures to allow effective evaluation of new compounds. Recent developments in animal models were presented, including high throughput approaches for drug screening. Novel and known DOI: 10.1002/jimd.12374