BLS Seminar Series- Simon Johnson, Academy of Medical Sciences Professor in Northumbria University

Seminar Abstract: Genetic mitochondrial diseases are estimated to impact over 1 in 4,000 individuals. These are an incredibly complex group of disorders, both genetically and clinically. Clinically, mitochondrial diseases are grouped by clinical presentation into over a dozen individual named clinical syndromes. For example, Leigh syndrome is the most common paediatric clinical presentation of genetic mitochondrial disease and is clinically defined by the presence of symmetric, progressive, neuroinflammatory lesions in specific brain regions and associated neurological symptoms, but disease typically includes a range of other symptoms such as seizures and metabolic dysfunction. Genetically, mitochondrial diseases are extremely heterogeneous - over 400 individual genes have been causally linked to mitochondrial diseases overall, over 110 linked to Leigh syndrome alone.
Given the genetic and clinical heterogeneity, treatments targeting single genetic defects are generally neither economically nor scientifically practical for individual mitochondrial disorders. Gene therapy, for example, which is estimated to cost well over £1 billion per gene targeted and many years to reach the market, cannot be viewed as a feasible approach to a set of diseases with over 400 genetic causes and very few patients per gene. Furthermore, gene therapy for diseases arising from mitochondrial DNA defects is not technologically possible. Similarly, trialing drugs for individual disorders can be extremely difficult when individual clinical syndromes are so rare. If stratified by genetic cause the issue is even more dire, with many causes de novo mutations and many n of 1 diseases. Finally, our limited understanding of the pathobiology of mitochondrial disease has greatly limited all of these efforts - for example, gene therapy requires knowledge of what the disease-causing cell type is in order to target treatments. As a case in point, only recently has work in Leigh syndrome revealed that the entire disease arises from neurones, and that key symptoms arise from distinct neuronal populations. Finally, targeting mitochondria presents unique challenges,
My group’s research is focused on deciphering the mechanisms underlying disease pathogenesis in mitochondrial disease, with a particular interest in identifying common disease pathways involved in disease presentation. In recent work, we have discovered that Leigh syndrome is an immune-mediated disease, and that immune- targeting interventions can prevent disease without the need for targeting the causal mitochondrial defect. In this talk I will discuss these findings, our ongoing efforts to decipher the mechanisms of immune activation in mitochondrial disease, and approaches to drug screening that we have recently begun undertaking using novel approaches in C. elegans models.
Biosketch: Professor Simon Johnson is an Academy of Medical Sciences Professor in Translational Bioscience at Northumbria University. Simon graduated from Oregon State University with a BSc in Biochemistry and Biophysics which was followed by a PhD in Molecular Basis of Disease/Pathology at the University of Washington, Seattle, USA. Following postdoctoral training at Albert Einstein College of Medicine, Bronx, USA and Seattle Children’s Research Institute, Seattle, USA, he joined the University of Washington and the Center for Integrative Brain Research Seattle Children’s Hospital in Seattle (USA) as an Assistant Professor in Neurobiology and Principal Investigator. He is the recipient of several prestigious awards. Among those, he was awarded twice with the Kelsey Wright Award for Excellence in Mitochondrial Medicine awarded by the Mitochondrial Medicine Society in 2022 and 2023 and most recently with an Academy of Medical Sciences Professorship in 2023 which facilitated his recruitment to the UK.
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