Graft Arterisosclerosis (Abbreviation: GA; Synonym: Transplant Vaculopathy) is not an autoimmune disease but a progressive and chronic form of vascular obliteration affecting only the arteries of solid organ transplants. It starts as early as three months after transplantation. Due to development of graft arteriosclerosis the survival of solid transplanted organs is at risk and limited.
The key morphological lesion of chronically failing organ transplants of e.g. heart, kidney or liver is a concentric myointimal hyperplasia of blood vessels of particularly the conduit arteries affecting the entire vasculature of the transplanted organ. Late transplant failure is a result of widespread ischemic injury to the transplanted organ, rather than damage induced by the immune system.
Interferon gamma (hIFN-y) is a key effector in graft arteriosclerosis.
The primary cellular source of hIFN-y are Th1 cells and natural killer cells of the innate immune system. Expansion of circulating Th1 cells is associated with endothelial dysfuntion prediciting graft arteriosclerosis after cardiac transplantation. The absence of IFN-y avoids graft arteriosclerosis development.
It is concluded from clinical and experimental data that a therapy for graft arteriosclerosis should focus on reducing synthesis or activity of hIFN-y. TIGO's recombinant receptor antagonists to human interferon gamma meet the latter requirement, i.e. activity reduction.
Market Graft Arteriosclerosis
Annually approx. 4.000 cardiac transplantations are performed in the western hemisphere.
Patient survival half life is 10 years.
Taking into account the annual number of cardiac transplantations and the survival half life, approx. 30.000 patients live currently with a donor heart.
The major reason for long-term transplant failure is graft arteriosclerosis (GA). The only cure for such failure is re-transplantation with a new donor heart.
Due to the immense costs of heart transplantation (~100 - 150 k€) and related medication (>25 k€ p.a.) and due to the shortage of donor organs for transplantation and re-transplantation, an effective and safe treatment for graft arteriosclerosis is of significance.
Since graft arteriosclerosis can be recorded as early as three months after transplantation, the therapy of choice is an early intervention to prevent GA.