Allogeneic HSCT transfers wild‐type cystinosin to nonhematological epithelial cells in cystinosis: First human report. Issue 11 (21st August 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: American journal of transplantation. Volume 18:Issue 11(2018)
• Page Start: 2823
• Page End: 2828
• Publication Date: 2018-08-21
• Subjects: bone marrow/hematopoietic stem cell transplantation -- clinical research/practice -- genetics -- graft‐versus‐host disease (GVHD) -- immunohistochemistry -- kidney disease: metabolic -- molecular biology: mRNA/mRNA expression -- pediatrics -- translational research/science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15029
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : Hematopoietic stem cell transplantation in patients with the lysosomal storage disorder cystinosis transfers wild‐type cystinosin mRNA and protein to nonhematopoietic tissues, resulting in decreased cystine crystal burden.