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
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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