Idogen´s technology aims at developing tolerant dendritic cells that are programmed for defined molecules or antigens. Idogen´s treatment method can be adapted to various diseases through small changes. In autoimmune diseases, the body’s immune system fights self-antigens, which could be avoided by reprogramming the immune system with Idogen´s technology.
Idogen has demonstrated the technology´s potential in several proof-of-concept studies. Idogen has successfully managed to re-program human white blood cells to tolerogenic dendritic cells as well as demonstrate in an animal model of Hemophilia A that treatment with tolerant dendritic cells results in a decreased incidence of inhibitory factor VIII antibodies and that the treatment has a long-term effect. Idogen has also shown “proof-of-principle” in type 1 diabetes and rheumatoid arthritis, by delaying or preventing transplant rejection, as well as delaying disease progression in animal models.
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 be tolerogenic dendritic cells. After treatment with zebularine in vitro, the dendritic cells have 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 cell therapy.
Proof-of-concept in a haemophilia A model
In 2015, Idogen initiated 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 cell therapy provides protection against the formation of inhibitory antibodies in patients with hemophilia A.
Proof-of-principle in a diabetes type I transplantation model
Idogen has achieved “proof-of-principle” in transplantation for diabetes type-1. In 2013 a study in diabetic rats was published, with two groups of nine rats receiving an 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 a rheumatoid arthritis model
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. In dendritic cells, this is understood to induce IDO1 expression and direct them towards inducing immunological tolerance versus the antigen collagen, which in this model accounted for the self-antigen responsible for the arthritis development.