Research Focus

  • Our research team in the US will be developing a liver organoid model* using patient cells to mimic what happens in OTCD.
  • Our research collaborator in Australia will be conducting preliminary experiments to investigate a potential stem cell therapy** using maternal cells to cure OTCD.

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 cells from patients with OTCD can be used for testing different treatment options for patients with the disease.
 
**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 and also cells which have the mutated OTC gene, we can select the ‘healthy cells’ for transplant in patient.