Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis: First human report

Mohamed A Elmonem, Koenraad Veys, Fanny Oliveira Arcolino, Maria Van Dyck, Maria C Benedetti, Francesca Diomedi-Camassei, Gert De Hertogh, Lambertus P van den Heuvel, Marleen Renard, Elena Levtchenko

Research output: Contribution to journalArticle

Abstract

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 have lysosomal cystine accumulation in various tissues, leading to cellular stress and damage, particularly in the kidney, cornea, and other extrarenal 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 extrarenal complications. Furthermore, the drug has severe adverse effects that significantly reduce patient compliance. Allogeneic hematopoietic stem cell transplantation (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 HSCT could be a curative treatment alternative to cysteamine therapy. We treated a 16-year-old boy who had 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 nonhematological 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.

Original languageEnglish
Pages (from-to)2823-2828
Number of pages6
JournalAmerican Journal of Transplantation
Volume18
Issue number11
DOIs
Publication statusPublished - Nov 2018

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Cystinosis
Cystine
Hematopoietic Stem Cell Transplantation
Cysteamine
Epithelial Cells
Inborn Errors Metabolism
Membrane Transport Proteins
Therapeutics
Patient Compliance
Lysosomes
Cornea
Renal Insufficiency
Disease Progression
Kidney
Amino Acids
Messenger RNA
Survival
Enzymes
Pharmaceutical Preparations
Proteins

Cite this

Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis : First human report. / Elmonem, Mohamed A; Veys, Koenraad; Oliveira Arcolino, Fanny; Van Dyck, Maria; Benedetti, Maria C; Diomedi-Camassei, Francesca; De Hertogh, Gert; van den Heuvel, Lambertus P; Renard, Marleen; Levtchenko, Elena.

In: American Journal of Transplantation, Vol. 18, No. 11, 11.2018, p. 2823-2828.

Research output: Contribution to journalArticle

Elmonem, MA, Veys, K, Oliveira Arcolino, F, Van Dyck, M, Benedetti, MC, Diomedi-Camassei, F, De Hertogh, G, van den Heuvel, LP, Renard, M & Levtchenko, E 2018, 'Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis: First human report', American Journal of Transplantation, vol. 18, no. 11, pp. 2823-2828. https://doi.org/10.1111/ajt.15029
Elmonem, Mohamed A ; Veys, Koenraad ; Oliveira Arcolino, Fanny ; Van Dyck, Maria ; Benedetti, Maria C ; Diomedi-Camassei, Francesca ; De Hertogh, Gert ; van den Heuvel, Lambertus P ; Renard, Marleen ; Levtchenko, Elena. / Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis : First human report. In: American Journal of Transplantation. 2018 ; Vol. 18, No. 11. pp. 2823-2828.
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