(2024) Future Treatments of PFIC

Future Treatments of PFIC

2024 PFIC Family & Scientific Conference Family Session

Speaker: Dr. Akihiro Asai. Click to read more about Dr. Asai!


My research focus is to develop an effective treatment for inherited cholestasis syndromes by using innovative disease-modeling platforms. We use patient-specific induced Pluripotent Stem Cells (iPSCs) to recapitulate human liver diseases by a cutting-edge method to generate “a liver in the dish.” We have established technologies to induce hepatic differentiation into iPSCs and achieved the robust hepatocellular function of bile acid synthesis and transport.

Notably, we have successfully modeled Progressive Familial Intrahepatic Cholestasis type 2 (BSEP deficiency), a representative genetic cholestatic disorder, within our experimental system. This research has unveiled novel pathophysiological mechanisms in this genetic condition, as detailed in our publication in Stem Cell Reports (2020). Furthermore, we have extended our disease modeling efforts to another prototypic genetic cholestatic disorder, PFIC type 4 (TJP2 deficiency), using similar yet refined methodologies. Our research findings, reported in Journal of Hepatology Reports (2022), reveal that TJP2 deficiency in induced hepatocytes (iHep) disrupts cellular polarity when cultured in a monolayer system. These discoveries provide a solid foundation for our current research proposal. 

In addition to my basic science research, I actively participate as a co-investigator in four clinical studies at our institution, focusing on treatments for HBV and HCV in children, as well as the management of PFIC and pediatric acute liver failure. Additionally, I serve as a site investigator for the LOGIC study, a longitudinal investigation into the genetic causes of intrahepatic cholestasis, as part of the NIH-funded Childhood Liver Disease Network.

After completing my clinical training to become a pediatric gastroenterologist, I joined Dr. Bezerra’s research laboratory at Cincinnati Children’s Hospital Medical Center (CCHMC) as a research fellow. I advanced bench scientific skills and knowledge under the instruction of Drs. James Wells, Takanori Takebe, Jorge Bezerra, Lee Denson, and Stacey Huppert. I have utilized their expertise to master the skills of stem cell culture to investigate cell-cell interaction during hepatocyte differentiation (Development, 2017).

In 2016, after completing a one-year clinical fellowship in advanced pediatric transplant hepatology at CCHMC, I joined the faculty of pediatric gastroenterology, hepatology, and nutrition as a physician-scientist and started my independent research laboratory. With secured funding from pilot initiatives and internal research funding, I established an independent research program composed of experts at CCHMC. I have benefitted from the productive environment of CCHMC to interact and collaborate with colleagues in the clinical and basic science realm to address questions that are timely and utilize cutting-edge technology in stem cell biology (Gastroenterology, 2020). 

Current treatments for PFIC can help with symptoms caused by the disease, and can slow the disease progression in some, but they don’t fix the root issue: a mutation in one’s genes that causes PFIC disease. Scientists are exploring a potential future where new treatments are designed to fix this root issue, but those treatments come with new risks. It is also important to understand that not every type of PFIC can be treated in the same way, since each subtype of PFIC is the result of a unique type of genetic mutation. In this talk, we’ll learn about potential new treatments for PFIC. We’ll learn why they’re different from what we have now, how they might vary among PFIC subtypes, and what risks they may carry.

This presentation was recorded at the 2024 PFIC Family & Scientific Conference hosted in partnership with Cincinnati Childrens Hospital. Find out more about PFIC Network Conferences!