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SUMMARY:Exploring the role of immune system as a primary driver of patholo
 gy in the mitochondrial disease Leigh syndrome - Professor Simon Johnson (
 University of Northumbria)
DTSTART:20241023T140000Z
DTEND:20241023T150000Z
UID:TALK220378@talks.cam.ac.uk
CONTACT:Lisa Arnold
DESCRIPTION:Leigh syndrome is the most common paediatric presentation of g
 enetic mitochondrial disease. Patients are typically born healthy\, with s
 igns disease most often appearing within the first few years of life. Leig
 h syndrome is a particularly devastating clinical presentation of mitochon
 drial disease\, with multi organ system involvement and major metabolic an
 d neurologic sequelae such as lactic acidosis and seizures. The defining f
 eature of Leigh syndrome is the appearance of symmetrically located progre
 ssive necrotising lesions in the brainstem\, which are the ultimate cause 
 of death. Given that over 110 distinct genes are causally linked to Leigh 
 syndrome\, with no clear overarching functional links (apart from localisi
 ng to the mitochondria)\, putative gene-specific therapies would impact on
 ly small subsets of patients. Accordingly\, unraveling the mechanisms invo
 lved in disease pathogenesis downstream of mitochondria function appears t
 o be the most promising avenue for therapeutic intervention.\n\nOur labora
 tory has been studying the mechanisms underlying the pathogenesis of Leigh
  syndrome with this goal in mind. Our studies have focused on understandin
 g two particularly striking features of the disease: 1) the curious post-n
 atal onset of disease symptoms and 2) the progressive\, symmetric\, neuroi
 nflammatory lesions which are the defining features of the disease. \n\nIn
  this talk\, I will discuss our recent work which demonstrates that Leigh 
 syndrome is an immune-mediated disease\, and discuss our ongoing studies a
 imed at further unraveling the steps that lead to immune activation and re
 cruitment to the brain lesion sites. Most remarkably\, we’ve found that 
 Leigh syndrome symptoms in the Ndufs4(-/-) mouse model can be prevented in
  mice by targeting the immune system\, without targeting mitochondrial fun
 ction. In addition\, activated peripheral macrophages drive central nervou
 s system lesions. These data reframe our understanding of how primary defe
 cts in mitochondrial function lead to pathology and open new avenues for t
 herapeutic intervention.
LOCATION:MRC MBU\, Level 3 Lecture Theatre\, The Keith Peters Building\, C
 B2 0XY
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