Pan-PPAR agonists

PPARs are being extensively investigated in the treatment of NAFLD/NASH.

In light of current knowledge of the various functions of PPARs, it can be speculated that activation of PPARα, PPARδ and PPARγ may be an effective therapeutic approach to prevent the development and progression of NASH through a combination of metabolic, anti-inflammatory and antifibrotic effects, thereby addressing a large spectrum of parameters involved in the disease along its continuum.

Given the hypoglycaemic, hypocholesterolaemic, antifibrotic, anti-inflammatory and vascular effects of PPARs, the use of agents that activate all three PPAR isoforms, so-called pan-PPAR agonists, is expected to lead to greater improvement in efficacy compared with targeting a single or dual PPAR isoform and may bring an innovative and efficacious therapeutic approach to prevent the development and progression of NASH, providing that side effects such as oedema, weight gain, bone fractures and cardiotoxicity observed with more selective PPAR agonists are absent or limited.

PPAR agonists being investigated in NASH

References

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