Research Focus

  • We have partnered with The Clevers Group in the Netherlands, led by Dr. Hans Clevers, to build a liver organoid model* with OTCD, mutation R26Q (c.77G>A). This research project launched in December of 2024 by scientist, Dr. Hanxiao Chen at the Hubrecht Research Institute. This model enables us to study the mechanism of action (what happens, and why) for different OTCD mutations, to identify more personalized treatment options for patients.
  • We are working with a research collaborator in Australia, Dr. Katie Beshant Day, to conduct preliminary experiments focused on a potential stem cell therapy** for OTCD using maternal cells. The experiments may help identify new pathways for modelling the disease/specific mutations in an efficient and timely manner, and also, potentially lead to a discovery of a curative treatment for OTC Deficiency using cell-therapy. 

Liver Organoid

The liver organoid is a helpful tool for modelling diseases such as OTCD, and examining different genetic variants to understand the underlying mechanism. This model will be used to conduct a comprehensive drug screen and test novel therapies that can effectively target our mutation (c.77 G>A), to increase OTC enzymatic activity in the liver.  

Stem Cell Therapy

We are currently exploring a cell therapy approach for OTCD using maternal cells from breast milk, specifically stem cells. We are in the process of launching preliminary experiments using such cells (breast milk-derived stem cells) to create a proof-of-concept model, which will help confirm whether this approach has any potential benefit. 

Drug Repurposing

CureOTCD has partnered with the University of Alabama Precision Medicine Institute (PMI) to help leverage AI data to identify potential drugs that can be repurposed for OTCD. The team at the University of Alabama has identified two specific drugs that may help increase expression of OTC enzyme in the liver: bucladesine and levothyroxine.

*Need for liver organoids:
 
The human liver is a complex organ that consists of different cell types with distinct functions. Liver cell models are limited because they do not allow examination of the entire organ and interplay between its different cell types. Liver organoids grow outside of the body and resemble the human liver in cell composition and functions. Liver organoids developed from patient cells can be used to test different treatment options.
 
**Stem cell therapy:
 
Liver cell transplant is not a new therapy for treating OTCD. In fact, there were clinical trials conducted about 10 years ago, and most recently in Japan, looking at transplanting liver cells into patients with OTCD via an injection to the portal vein. The treatment has not been clinically approved and the approach is used as a “bridge to therapy,” not a cure. Our team will be looking to confirm whether stem cells derived from the mother (source: breastmilk) produce functional urea cycle and have OTC activity in differentiated liver cells, called hepatocytes. Since women have cells containing the healthy OTC gene activated and also cells which have the mutated OTC gene activated, we can select the ‘healthy cells’ for transplant in patients.