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Published on: March 28, 2018
New Therapeutic Targets in Autoimmune Cholangiopathies
Alessio Gerussi1,2, Martina Lucà1,2, Laura Cristoferi1,2
1Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
Abstract:
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the "leaky gut" hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.
Insights
New targeted drugs show promise for autoimmune liver diseases like primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Research focuses on molecular pathways to develop effective treatments for these rare conditions.
Area of Science:
- Hepatology
- Immunology
- Gastroenterology
Background:
- Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare autoimmune liver diseases with limited therapeutic options.
- Understanding the underlying molecular mechanisms is crucial for developing targeted treatments.
Purpose of the Study:
- To review the current understanding of molecular mechanisms in PBC and PSC.
- To highlight actionable biological pathways for novel therapeutic development.
Main Methods:
- Review of current literature on PBC and PSC pathogenesis.
- Focus on molecular pathways and emerging targeted therapies.
- Discussion of clinical trials and novel treatment approaches.
Main Results:
- For PBC, farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) pathways are key targets for choleretic and anti-inflammatory drugs.
- For PSC, emerging theories involve "leaky gut," dysbiosis, and bile acid toxicity, leading to treatments targeting lymphocyte trafficking, microbiota, and bile acids.
- Antifibrotic agents are under investigation for both diseases.
Conclusions:
- Targeted therapies based on a deeper understanding of molecular pathways offer new hope for PBC and PSC patients.
- Novel treatments are emerging, addressing specific pathogenetic mechanisms in these autoimmune cholangiopathies.
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