Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Japanese boy aged 2 years 11 months with late infantile metachromatic leukodystrophy underwent bone marrow transplantation (BMT) from his human leukocyte antigen (HLA) identical but mixed lymphocyte culture reactive father. Chimerism and increased arylsulfatase A activities of leukocytes had been observed with retarded progression of neurological deterioration during the first 3 months post-BMT. Graft rejection gradually occurred and donor cells were almost completely eliminated from the patient at 1 year after BMT. The process of neurodegeneration progressed clinically and neuroradiologically. Three possible reasons for the pathogenesis of graft rejection are: (i) T cell depletion of donor marrow cells as graft-versus-host disease (GVHD) prophylaxis; (ii) a slightly weak conditioning regimen: and (iii) a small number of marrow cells transplanted. It is stressed that as BMT is still a preliminary therapy for metachromatic leukodystrophy indications, conditioning, and GVHD prophylaxis for BMT should be considered individually.
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PMID:Bone marrow transplantation for late infantile metachromatic leukodystrophy: pathogenic investigation for graft rejection. 825 24

The possibility of using umbilical cord blood for transplantation in several enzyme deficiencies has received increasing attention because of the availability of cord blood, the reduced incidence of post-transplantation complications, such as graft-versus-host disease and the possible accomplishment of good corrective results following transplantation, even in cases of greater HLA disparity. The use of hematopoietic stem cells from unrelated donors is even more highly recommended for the treatment of inherited enzyme deficiencies, because it might reduce the risk of the transplanted cells originating from a carrier of the defect, which might have an inadequate corrective ability. Our study was designed to elucidate whether the gestational age and mode of delivery influences the arylsulfatase-A activity in the umbilical cord blood. Enzyme activities proved to be similar in the four populations studied (full-term normal spontaneous vaginal delivery, full-term caesarean section, preterm normal spontaneous vaginal delivery and preterm caesarean section). Therefore, umbilical cord blood samples seem to be suitable for transplantation in metachromatic leukodystrophy, regardless of gestational age and mode of delivery. Moreover, our results are the first published data on normal values for arylsulfatase-A activity in human umbilical cord blood.
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PMID:Arylsulfatase-A in umbilical cord blood: gestational age and mode of delivery do not influence enzyme activity. 1196 Feb 67

Nowadays, different treatment options are available for an extending list of lysosomal storage diseases (LSDs). Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. Enzyme replacement therapy has been developed recently for MLD, and a Phase I/II trial is ongoing. However, the blood-brain barrier limits the access of the recombinant product to the nervous tissues. Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a quantitatively more effective source of functional enzyme than normal donor cells when transplanted in patients with MLD, thus possibly overcoming the limits of HSCT. Moreover, autologous transplantation might be associated with a significantly reduced transplant-related morbidity and TRM avoiding the risk of GVHD. Therefore, such a gene therapy strategy could represent a significant advance in comparison to conventional allogeneic HSCT.
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PMID:Metachromatic leukodystrophy: an overview of current and prospective treatments. 1897 39