Allogeneic HSCT transfers wild-type cystinosin to nonhematological epithelial cells in cystinosis: First human report
Autor: | Marleen Renard, Gert De Hertogh, Lambertus P. van den Heuvel, Maria Van Dyck, Mohamed A. Elmonem, Koenraad Veys, Fanny Oliveira Arcolino, Elena Levtchenko, Francesca Diomedi-Camassei, Maria Chiara Benedetti |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
pediatrics translational research/science medicine.medical_treatment Cystine Hematopoietic stem cell transplantation clinical research/practice metabolic [kidney disease] 03 medical and health sciences chemistry.chemical_compound All institutes and research themes of the Radboud University Medical Center Lysosome medicine Immunology and Allergy genetics Pharmacology (medical) bone marrow/hematopoietic stem cell transplantation Adverse effect graft-versus-host disease (GVHD) Transplantation Kidney business.industry medicine.disease Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] 030104 developmental biology medicine.anatomical_structure chemistry Cystinosin immunohistochemistry Cystinosis Cancer research Cysteamine mRNA/mRNA expression [molecular biology] business |
Zdroj: | American Journal of Transplantation, 18, 11, pp. 2823-2828 American Journal of Transplantation, 18, 2823-2828 |
ISSN: | 1600-6135 2823-2828 |
Popis: | 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. ispartof: AMERICAN JOURNAL OF TRANSPLANTATION vol:18 issue:11 pages:2823-2828 ispartof: location:United States status: published |
Databáze: | OpenAIRE |
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