FK778 in Experimental Xenotransplantation: A Detailed Analysis of Drug Efficacy

Schrepfer, Sonja; Deuse, T.; Koch-Nolte, Friedrich; Krieger, Thorsten; Haddad, Munif; Schäfer, Hansjörg; Pelletier, Marc; Robbins, Robert C.; Reichenspurner, Hermann

doi:10.1016/j.healun.2006.10.013

Cited by 9 publications

(4 citation statements)

References 32 publications

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“…In recent years, due to the rapid technical development of molecular biology and immunology, the studies of pig‐to‐human heart xenotransplantation have become more and more active [2–6]. The immunological aspects of xenotransplantation have been studied in considerable detail but, with the exception of discrepancies in coagulation, which plays a major role in xenograft failure [7], less emphasis has been given to investigations of biomechanical properties of pig organ systems and their compatibility with those of humans.…”

Section: Introductionmentioning

confidence: 99%

Biomechanical properties of ascending aorta and pulmonary trunk in pigs and humans

Yu²,

Zhang³

et al. 2008

Xenotransplantation

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Section: Introductionmentioning

confidence: 99%

Biomechanical properties of ascending aorta and pulmonary trunk in pigs and humans

Yu²,

Zhang³

et al. 2008

Xenotransplantation

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“…Malononitrilamide (FK778), the active metabolite of leflunamide A77 1726, inhibits both T‐cell and B‐cell function by acting on de novo pyrimidine synthesis. FK778 has been tested in intestinal transplantation in pigs (52) and in cardiac transplantation in rats (53). Acute rejection was absent or mild.…”

Section: New Drugsmentioning

confidence: 99%

Calcineurin inhibitor minimization in pediatric liver allograft recipients

Olio

Kelly

2009

Pediatric Transplantation

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The use of CNI in pediatric LTx has dramatically improved the outcome for children with end-stage liver disease by significantly reducing the rate of acute and chronic rejection. Long-term concerns about CNI-induced nephrotoxicity and other adverse effects remain an issue, particularly as the emphasis moves from short-term survival to long-term quality of life. This review summarizes lessons learnt from pediatric and adult solid organ transplantation in minimizing CNI use in immunosuppression protocols in children following LTx. There are three models for CNI minimization: dose reduction, withdrawal or avoidance, supplemented by the use of IL-2 receptor blocking antibodies in the peri-transplant period, and early transition to alternate drugs such as MMF or SRL. Prospective studies evaluating reduction or withdrawal protocols in adult and pediatric LTx indicate that rejection rates are comparable with traditional CNI-based immunosuppression and that two and five yr patient and graft survival are similar, with recovery in renal function. There are few studies evaluating complete avoidance of CNI, apart from that in renal transplantation, although the benefits of long-term reduction in cardiovascular, metabolic, and possibly neoplastic side effects may justify this approach. It is not clear yet how CNI minimization will affect the development of tolerance but experimental and preliminary clinical studies indicate that CNI and steroid avoidance or minimization in the peri-operative period may favor the development of long-term graft tolerance. In summary, CNI minimization may be safe and effective in the short term but large-scale pediatric randomized studies are required to evaluate the long-term efficacy of these regimes in the development of chronic rejection, PTLD, and graft tolerance.

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“…Schrepfer et al studied the effect of FK778 (a leflunomide analog) in concordant hamster-to-rat aortic xenotransplantation [20]. Recipients were treated for 14 days with FK778, tacrolimus, sirolimus alone, or a combination regimen.…”

Section: Immunobiologymentioning

confidence: 99%