Diseases of the Immune System

Organ transplantation as a treatment for end stage renal, heart, lung, liver and pancreas failure subsequently requires lifelong immunosuppressive treatment. Current drugs have serious side effects and better drugs are needed to decrease this morbidity. All new drugs have to be evaluated in a non human primate model, as results from rodent models are not sufficient to predict their effect in humans.

Many of the organ transplantation protocols that are in current clinical use were developed following research at the BPRC. For example T-cell depletion can lead to better acceptance of a transplanted organ. Following evaluation of T-cell depletion in monkeys, modified protocols were accepted for evaluation in humans.

SDZ-RAD (Certican®) is a new immunosuppressive remedy for post-operative treatment of transplantation patients. SDZ-RAD was tested and found to be relatively safe and effective in monkeys. These results supported the clinical evaluation of SDZ-RAD. These clinical trials also gave promising results so that the product is now awaiting registration.

In preparation for planned clinical trials in the Netherlands, new protocols with the potential to improve the success of transplantation using currently available drugs were tested in monkeys. The results of these tests did not meet expectations so that plans for these clinical trials were abandoned. However, new approaches are continuously being developed employing new drugs as well as new combinations of existing drugs. The BPRC contributes to this process with new methods for analysis and collaborative research with drug developers. An example is the demonstration of the expression of the cytokine TGF-beta in grafts which are successfully tolerated.

Bone marrow transplants (BMT) are often required for patients with either cancerous or non-cancerous disorders of the blood. New, safer bone-marrow transplantation protocols have been developed in collaborations between hospitals and BPRC. These protocols are in current clinical use.

A major complication of BMT is often Graft versus Host disease (GVHD). Techniques to manipulate the microflora (the bacteria that live inside the gut) of the transplant recipient have been developed at the BPRC. These techniques can help to prevent GVHD and are currently in clinical use in several hospitals.