Pioglitazone, a selective agonist of the nuclear PPAR-γ receptors, was evaluated in a phase I trial involving 13 patients with inclusion body myositis, all of whom received the treatment for 8 months following a 4-month observation period. This trial aimed to demonstrate the proof of concept for the benefits of a treatment targeting the molecular pathways involved in mitochondrial function.
- Dysregulations in mitochondrial muscle metabolites were identified in patients prior to treatment.
- The primary endpoint was not met: the expression levels of the PPARGC1A gene and other genes involved in mitochondrial pathways were not significantly altered by pioglitazone. Nevertheless, a trend towards an increase was observed.
- Pioglitazone appears to favourably modulate mitochondrial metabolism in affected muscles, with a profile similar to that of healthy subjects.
- A slowing of functional decline was observed in four patients.
- The safety profile of pioglitazone was similar to that reported in other conditions.
- The trial was terminated prematurely due to the Covid-19 pandemic.
These results support research into the pharmacological targeting of mitochondrial pathways and the conduct of further studies to assess the clinical efficacy of pioglitazone.
