Allogeneic HSCT transfers wild type cystinosin to non-hematological epithelial cells in cystinosis: first human report.

Elmonem, M. A., K. Veys, F. O. Arcolino, M. van Dyck, M. C. Benedetti, F. Diomedi-Camassei, G. De Hertogh, L. P. van den Heuvel, M. Renard, and E. Levtchenko, "Allogeneic HSCT transfers wild type cystinosin to non-hematological epithelial cells in cystinosis: first human report.", American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2018 Jul 21.


Cystinosis is an autosomal recessive lysosomal storage disorder characterized by the defective transport of the amino acid cystine out of the lysosome due to a deficiency of cystinosin, the lysosomal cystine transporter. Patients suffer from lysosomal cystine accumulation in various tissues, leading to cellular stress and damage, particularly in the kidney, cornea, and other extra-renal tissues. Cysteamine, a cystine-depleting agent, improves survival and delays the progression of disease, but it does not prevent the development of either renal failure or extra-renal complications. Furthermore, the drug has severe adverse effects that significantly reduce patient compliance. Allogeneic HSCT is currently established as a therapeutic option for many inborn errors of metabolism, where the main pathologic driving factor is an enzyme deficiency. Recent studies in the cystinosis mouse-model suggested that hematopoietic stem cell transplantation (HSCT) could be a curative treatment alternative to cysteamine therapy. We treated a 16-year-old male suffering from infantile cystinosis and side effects of cysteamine therapy with HSCT. We were able to demonstrate successful transfer of the wild type cystinosin protein and CTNS mRNA to non-hematological epithelial cells in the recipient, as well as a decrease in the tissue cystine-crystal burden. This is the first report of allogeneic HSCT in a patient with cystinosis, the prototype of lysosomal membrane-transporter disorders. This article is protected by copyright. All rights reserved.



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