Proof of concept in man, a world first, by treating three patients with HHALPC by Prof. Etienne Sokal and his team at Cliniques Universitaires Saint-Luc within the framework of the hospital exemption rules and the approval of the Ethic Committee.
Test doses of human adult liver stem cells HHALPC (Heterologous Human Adult Liver Progenitor Cells) have already been injected in three patients at St Luc Hospital (Brussels, Belgium). The cells were produced in the Liver Stem Cell Tissue Bank of Saint-Luc Hospital.
The first patient was suffering from ornithine transcarbamylase deficiency one of the 6 Urea Cycle defects, the second patient presented a Crigler-Najjar syndrome and the third patient was suffering from Glycogenosis type 1a. The infusion of the liver progenitor cells occurred safely and was well tolerated by the patients.
Achievements of the pre-clinical proof of concept in three different rodent models.
10 GLP/non GLP studies with HHALPC have been conducted in animals in order to assess engraftment of HHALPC as well as activation of the deficient enzyme (proof of concept studies), risk of tumorigenicity and biodistribution.
Three pre-clinical studies were undertaken in two immunodeficient micemodels with and without liver regeneration stimulus. These studies demonstrated that HHALPC (Heterologous Human Adult Liver Progenitor Cells), once injected in animals, are able to engraft and differentiate in the host liver parenchyma despite a xenogeneic environment. Besides engraftment, successful hepatic differentiation in situ was also demonstrated.
Another study demonstrated the functional proof of concept through restoration of in vivo enzyme activity on Gunn rats, an animal model homologous to Crigler Najjar Syndrome. Gunn rats present a high level of unconjugated bilirubin in blood due to a mutation in UGT1A1 gene similar to the human condition. Transplanted Gunn rats responded to Promethera® HepaStem therapy with a significant decrease of unconjugated bilirubin in blood after 6 months.
Successful technology transfer of manufacturing process from the Université Catholique de Louvain into a large scale facility located in Mont-Saint-Guibert.
The technology has been successfully transferred and scaled up from the university laboratory to the company. Promethera Biosciences has its own clean rooms and has now the capability of producing progenitor cells in view of clinical trials starting in 2012.
Patent granted by the European Patent Office in February 2011.
The first international patent application for HHALPC has been submitted in December 2005. The patent (EP 1969118) has been granted by the European Patent Office in February 2011 protecting this valuable asset for the company. The patent is under review in US and other countries of the world.
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