LRPPRC gene replacement therapy preserves cardiac function and prevents premature death in a mouse model of mitochondrial disease

Compact single rAAV9 gene replacement restored cardiac LRPPRC expression in heart and skeletal muscle-specific Lrpprc knockout mice, preserving OXPHOS function and markedly extending survival.

• Why it matters: LRPPRC pathogenic variants cause severe, incurable mitochondrial disease with neurological involvement plus hepatopathy or cardiomyopathy, and AAV delivery is constrained by the large LRPPRC coding sequence.
• What they did: The authors engineered compact single rAAV9 vectors carrying human or mouse LRPPRC and delivered them intravenously to heart and skeletal muscle-specific Lrpprc knockout mice.
• The result: Treated mice showed preserved oxidative phosphorylation function, prevention of cardiomyopathy, and markedly extended survival, with only partial skeletal muscle rescue.

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