Pioglitazone evaluated in inclusion body myositis during a phase I trial

Pioglitazone, a selective agonist of the nuclear PPAR-γ receptors, was evaluated in a phase IAu cours d’un essai clinique de phase I un médicament dont l’intérêt thérapeutique a été montré sur des modèles animaux et/ou cellulaires (essais précliniques) est administré pour la première fois à un petit groupe de volontaires sains, plus rarement à des malades, afin d’évaluer leur tolérance à la substance en fonction de la dose (Comment le futur traitement est-il absorbé et éliminé ? Comment se fait sa répartition dans les organes ? Est-il toxique et à quelles doses ? Existe-t-il des effets secondaires ?). 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.

Modifying muscle metabolic dysregulation in inclusion body myositis with pioglitazone: a single-arm trial. Adler B, Bene M, Zhang C et al. Nat Commun. 2026 Mar.