Why are PPAR agonists a promising option for the management of NASH ?
What is important in the treatment of NASH specifically, is that you take into account what happens outside the liver that has an impact on the liver. Some drugs in development are pure liver-centric drugs, with an effect only in the liver but other drugs have an impact on several mechanisms and organs outside the liver that subsequently also benefit the liver.
PPArs and the liver
In that context, the field of the PPARs is very important because we already know from older studies like treatments with PPAR agonist Pioglitazone that are used for the treatment of diabetes. They also have a positive impact on the liver. Not all PPARs are to the same extent but there is an impact on the liver and that impact is partially related to what the drug does inside the PPAR. It is also driven by what the drug does outside the liver, and why it is useful in the treatment of diabetes. So that notion of having drugs that not only target the liver but also target metabolic and inflammatory processes outside that subsequently may have a positive influence on what happens inside the liver. That’s one of the key elements of the expert panel and the PanNASH initiative.
One of the types of drugs that has potential of being a very valuable therapeutic option is a whole field of PPARs. There are several molecules in development. But what is most probably very promising is that you combine an effect on the three isotopes. You have the PPAR which are located in many different organisms and many different cell types. Combining the effect on several of these isotopes on several occasions is potentially very promising to treat the disease which is in the end part of a systemic disease. The liver is not isolated, it’s really something that is closely related to the rest of the body and several directions. It’s not just that the liver is suffering from what is happening outside the liver, but the liver is also contributing to the metabolic division. So it’s really a story of everything by tackling several mechanisms and several sites at the same time. You are more likely to achieve the substantial benefits than you when you are just picking out one specific mechanism at one specific side.