Idogen is based on the discovery that Zebularine can upregulate the enzyme IDO1 that inhibit immune reactions. Dendritic cells are a type of white blood cell that play a key role in the immune system as they regulate other immune cells recognition of what is native and foreign. When the dendritic cells present an antigen (substance that the immune system reacts against) for other immune cells, they control whether these will initiate an immune response or not. If the dendritic cells are activated, for example, by genetic material from bacteria, the dendritic cells steer the immune cells to start an immune response against the antigens they recognize. Tolerogenic dendritic cells treated according to Idogens technology will instead direct the immune cells to create a specific and sustained immune tolerance towards that specific antigen.
Proof-of-concept in human cells
Idogen has in a proof-of-concept study in human cells successfully managed to re-program human white blood cells to tolerogenic dendritic cells. The dendritic cells have in studies in vitro after zebularine-treatment successfully inhibited the activation of other immune cells. The experiments have been repeated with immune cells from several individuals. The results are an important milestone for the continued development of a tolerogenic vaccine.
Proof-of-concept in model of hemophilia A
Idogen initiated in late summer 2015 a ”proof-of-concept”-study of the company’s cell therapy in an animal model of hemophilia A with human factor VIII. The study results showed that treatment with tolerogenic dendritic cells results in reduced formation of factor VIII inhibitory antibodies and treatment has a prolonged effect. If the method can be transferred to humans it means that treatment with tolerogenic vaccine provides protection against formation of inhibitory antibodies in patients with hemophilia A.
Proof-of-principle in model of type I diabetes transplantation
Idogen has achieved “proof-of-principle” in transplantation for diabetes type-1. In 2013 a study was published in diabetic rats, with two groups of nine rats receiving insulin-producing cell transplant from a different strain. One group underwent two weeks of Zebularine-treatment from day six after transplantation whereas the control group was untreated. In the study, a statistically significant difference between the group treated with Zebularine and the control group was observed. The study was terminated on day 90. The figure below shows that the control group exhibited 100% allograft rejection after 40 full days and that the rejection was significantly delayed or completely prevented in the group treated with Zebularine (Nittby et al, PLOS ONE, 8: 1-8, 2013).
Proof-of-principle in model of rheumatoid arthritis
In an ongoing collaboration with Professor Richard Williams’s research group at the University of Oxford, the progression of rheumatoid arthritis was shown to be strongly inhibited in an animal model. These results were obtained when treating animals with Zebularine for a limited period, starting when they show early joint symptoms. Thereby all their various cell types were exposed to Zebularine. In dendritic cells, this is expected to induce IDO1 expression and direct them towards inducing immunological tolerance versus the antigen collagen, which in this model accounted for the antigen responsible for the arthritis-development.