MedicalResearch.com Interview with:
Stanley C. Jordan, M.D
Director, Division of Nephrology
Medical Director, Kidney Transplant Program
Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory
Cedars-Sinai, Los Angeles, CA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found.
The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: I feel the readers should understand that this is a very preliminary study however it is very encouraging since IdeS® is effective in eliminating donor specific antibodies totally. These antibodies create an impenetrable immunologic barrier to kidney transplantation thus preventing patient from receiving life-saving transplants. Further work will be needed to validate these results but this could significantly advance the field.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Our recommendations are to create studies that would compare IdeS® desensitization to standard of care using plasmapheresis+IVIG or IVIG + Rituximab as desensitization agents. We also feel studies of IdeS in heart, lung, and bone marrow transplant could be very helpful as well. Ultimately, it may find use in treated autoimmune diseases.
MedicalResearch.com: Is there anything else you would like to add?
Response: Certainly I feel that this work is a major step forward in desensitization. We feel that this drug has breakthrough potential in both prevention and treatment of antibody mediated rejection. After several decades of research with other agents it is clear that IdeS® has the most profound ability to alter existing antibody levels and allow transplantation to occur. Thank you. Disclosure: Dr. JJordan received consulting fees and research grants from Hansa Medical.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Stanley C. Jordan, M.D., Tomas Lorant, M.D., Jua Choi, Pharm.D., Christian Kjellman, Ph.D., Lena Winstedt, Ph.D., Mats Bengtsson, M.D., Xiaohai Zhang, Ph.D., Torsten Eich, M.D., Mieko Toyoda, Ph.D., Britt-Marie Eriksson, M.D., Shili Ge, Ph.D., Alice Peng, M.D., Sofia Järnum, Ph.D., Kathryn J. Wood, D.Phil., Torbjorn Lundgren, M.D., Lars Wennberg, M.D., Lars Bäckman, M.D., Erik Larsson, M.D., Rafael Villicana, M.D., Joe Kahwaji, M.D., Sabrina Louie, M.P.H., Alexis Kang, B.S., Mark Haas, M.D., Ph.D., Cynthia Nast, M.D., Ashley Vo, Pharm.D., and Gunnar Tufveson, M.D.
N Engl J Med 2017; 377:442-453
August 3, 2017 DOI: 10.1056/NEJMoa1612567
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