Alpha-Mannosidosis: Therapeutic Strategies.

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Term Occurence Count Dictionary
lysosomal storage disease 3 endocrinologydiseases
Fabry disease 1 endocrinologydiseases
Krabbe disease 1 endocrinologydiseases
X-linked adrenoleukodystrophy 1 endocrinologydiseases
alpha-mannosidosis 51 endocrinologydiseases
leukodystrophy 1 endocrinologydiseases

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Fabry disease 29956 become an alternative to ERT for alpha-mannosidosis in the near future, as has already observed for Fabry disease [[71]]. Pharmacological chaperons selectively bind to misfolded enzymes in the endoplasmic reticulum,
Krabbe disease 24020 alpha-mannosidosis mice. Other studies suggest that lysosomal enzymes may cross the BBB in animal models with Krabbe disease [[62]], metachromatic leucodystrophy [[63]], mucopolisaccharidosis type I [[64]], and mucopolisaccharidosis
X-linked adrenoleukodystrophy 13495 inherited metabolic diseases with associated neuronal dysfunction, such as Hurler syndrome and cerebral X-linked adrenoleukodystrophy [[45]]. In bone marrow transplantation, normal donor stem cells differentiate to different lineages
alpha-mannosidosis 1132 Similarly to other lysosomal storage diseases, there is no relationship between genotype and phenotype in alpha-mannosidosis . Enzyme replacement therapy is at the moment the most effective therapy for lysosomal storage disease,
alpha-mannosidosis 1264 replacement therapy is at the moment the most effective therapy for lysosomal storage disease, including alpha-mannosidosis . In this review, the genetic of alpha-mannosidosis has been described together with the results so far
alpha-mannosidosis 1315 therapy for lysosomal storage disease, including alpha-mannosidosis. In this review, the genetic of alpha-mannosidosis has been described together with the results so far obtained by two different therapeutic strategies:
alpha-mannosidosis 1592 therapy. The primary indication to offer hematopoietic stem cell transplantation in patients affected by alpha-mannosidosis is preservation of neurocognitive function and prevention of early death. The results obtained from
alpha-mannosidosis 1846 III study provide evidence of the positive clinical effect of the recombinant enzyme on patients with alpha-mannosidosis .1. IntroductionGlycoproteins are widely present within cells and cell surfaces. Two pathways are used
alpha-mannosidosis 3628 effects on cellular functions such as synaptic release, exocytose, and autophagy. Among glycoproteinoses, alpha-mannosidosis is caused by the deficiency of the lysosomal enzyme alpha-d-mannosidase (EC 3.2.1.24). Lysosomal α-mannosidase
alpha-mannosidosis 4102 B forms are the product of a single gene (MAN2B1), as demonstrated in the lysosomal storage disease alpha-mannosidosis (MIM 248500) in which both A and B are lacking [[5]]. This enzyme has been characterized and purified
alpha-mannosidosis 4883 (Felis catus) [[9]], and guinea pigs (Cavia porcellus) [[10]]. In addition to the natural occurring alpha-mannosidosis , the disease was induced experimentally with swainsonine in the sheep (Ovis aries) [[11]] and a mouse
alpha-mannosidosis 5013 disease was induced experimentally with swainsonine in the sheep (Ovis aries) [[11]] and a mouse model of alpha-mannosidosis was generated by homologous recombination [[12]]. The histological and biochemical characteristics underline
alpha-mannosidosis 5164 recombination [[12]]. The histological and biochemical characteristics underline the similarity between alpha-mannosidosis in human and mice, whereas the clinical presentations are different. The phenotype in the alpha-mannosidase
alpha-mannosidosis 5499 drastically increased urinary excretion of mannose-containing oligosaccharides, as observed in human alpha-mannosidosis . Neutral sugars are increased and oligosaccharides are accumulated in several tissues such as spleen,
alpha-mannosidosis 5657 oligosaccharides are accumulated in several tissues such as spleen, kidney, brain, and liver. This mouse alpha-mannosidosis model has been more useful than other models such as cat and cattle in terms of life span, ease of breeding
alpha-mannosidosis 5951 investigate the pathogenesis of the disease and to develop an enzyme replacement therapy (ERT) for alpha-mannosidosis .2. Inherited Deficiency of Alpha-Mannosidase (Alpha-Mannosidosis)Alpha-mannosidosis is a rare lysosomal
alpha-mannosidosis 6607 loss, skeletal deformities, central nervous system involvement, and immuno defects. Traditionally, alpha-mannosidosis has been classified in two groups: Type 1, with a mild phenotype including hearing loss, mental retardation,
alpha-mannosidosis 8547 diagnostic. In order to characterize the clinical features and disease progression of patients affected by alpha-mannosidosis , a longitudinal study was conducted on 43 patients from four different European countries [[15]]. The
alpha-mannosidosis 9074 determined. The longitudinal study was also conducted in order to assess the natural history of patients with alpha-mannosidosis and to evaluate short-term (24 months) changes in the disease parameters. Few retrospective studies
alpha-mannosidosis 9219 (24 months) changes in the disease parameters. Few retrospective studies on the clinical course of alpha-mannosidosis had been performed, and all of them included only a small number of patients [[17],[18],[19],[20],[21]].
alpha-mannosidosis 9615 Ataxia and mental retardation were the most noticeable findings observed in the study. All patients with alpha-mannosidosis , independently from age, showed hearing loss (bone and conductive). Minor ophthalmological abnormalities
alpha-mannosidosis 10397 results. The same conclusion has been obtained with the 3 min stair climb test. Patients affected with alpha-mannosidosis excrete high amounts of undegraded oligosaccharides in the urine and plasma that interestingly correlate
alpha-mannosidosis 12602 and its structure have allowed for the identification and characterization of many mutations causing alpha-mannosidosis [[34],[35],[36],[37],[38],[39],[40],[41],[42],[43]]. Very recently, all genetic variants in the MAN2B1
alpha-mannosidosis 13043 variants from 191 patients are present. All these data have greatly improved the molecular diagnosis of alpha-mannosidosis , but there is still no clear relationship between genotype and phenotype. The lack of a relationship
alpha-mannosidosis 14028 available therapeutic approach to enzyme replacement. HCT has been tested for the first time in cats with alpha-mannosidosis [[46]]. This study indicated that HCT can lead to significant levels of alpha-mannosidase within neurons
alpha-mannosidosis 14248 neurons of the central nervous system and to the compensation for the genetic metabolic defect. HCT for alpha-mannosidosis was first reported in two patients: one patient died 18 weeks after transplantation [[47]], whereas
alpha-mannosidosis 14739 effects were obtained. Two additional studies on HCT have been reported: one on four patients with alpha-mannosidosis [[49]] and the second one was the first patient who received a T-cell-depleted peripheral blood stem
alpha-mannosidosis 14892 first patient who received a T-cell-depleted peripheral blood stem cell transplantation (PBSCT) for alpha-mannosidosis [[50]]. All four patients received unrelated donor graft. All four patients showed normalization of
alpha-mannosidosis 15611 development. The mother was chosen as stem cell donor despite the fact that she was a heterozygous carrier of alpha-mannosidosis with enzyme activity levels below normal. Therefore, heterozygous carriers (i.e., parents and siblings)
alpha-mannosidosis 15867 donors. The effects of early and late bone marrow transplantation has been tested in two brothers with alpha-mannosidosis [[51]]. The older brother underwent transplantation at 13 years for the treatment of increasing somatic
alpha-mannosidosis 16756 was excellent. More recently, a successful unrelated bone marrow transplantation in two siblings with alpha-mannosidosis has been reported [[52]]. In both siblings, enzyme levels reached normal limits, and improvements in
alpha-mannosidosis 16979 clinical symptoms were recognized early after HCT. The largest retrospective analysis of patients with alpha-mannosidosis after HCT has been reported by Mynarek [[53]]. It has been shown that HCT in patients with alpha-mannosidosis
alpha-mannosidosis 17089 alpha-mannosidosis after HCT has been reported by Mynarek [[53]]. It has been shown that HCT in patients with alpha-mannosidosis is a feasible therapeutic option. The mortality and morbidity after HCT was comparable to other diseases.
alpha-mannosidosis 17581 patients without a total resolution of hearing disability. The most important clinical problem for alpha-mannosidosis patients was their deficiency in hearing and expressive speech. Stabilization or even improvement of
alpha-mannosidosis 17911 abnormalities in the growing skeleton. The primary indication to offer HCT in patients affected by alpha-mannosidosis is the preservation of neurocognitive function and the prevention of early death. The morbidity and
alpha-mannosidosis 18098 early death. The morbidity and mortality rate associated with HCT must be balanced. In the case of alpha-mannosidosis specific values for transplantation-related mortality rates are not available. Patients who have received
alpha-mannosidosis 18567 Hurler’s disease [[56]]. In conclusion, HCT should be considered a therapeutic approach in patients with alpha-mannosidosis .5. Enzyme Replacement TherapyIn January 2018, the European Medicines Agency’s (EMA) committee for
alpha-mannosidosis 19474 mistargeting of enzymes rather than lysosomes, and intractable tissues. The beginning of the ERT for alpha-mannosidosis dates back to 2004, when its efficacy was tested in alpha-mannosidosis mice [[58]] that were generated
alpha-mannosidosis 19545 The beginning of the ERT for alpha-mannosidosis dates back to 2004, when its efficacy was tested in alpha-mannosidosis mice [[58]] that were generated by homologous recombination [[12]]. The generation of a mouse model
alpha-mannosidosis 19668 [[58]] that were generated by homologous recombination [[12]]. The generation of a mouse model for alpha-mannosidosis and the production of the recombinant alpha-mannosidase have made it possible to study the efficacy
alpha-mannosidosis 19797 production of the recombinant alpha-mannosidase have made it possible to study the efficacy of ERT in alpha-mannosidosis . Homozygous mutant mice show alpha-mannosidase deficiency and elevated urinary secretion of mannose
alpha-mannosidosis 20469 topographical distribution, as well as the biochemical alterations, closely resemble those reported for human alpha-mannosidosis . Therefore, the mouse model for alpha-mannosidosis is a suitable tool to study the phatophysiology of
alpha-mannosidosis 20520 alterations, closely resemble those reported for human alpha-mannosidosis. Therefore, the mouse model for alpha-mannosidosis is a suitable tool to study the phatophysiology of the disease and to develop therapeutic strategies.
alpha-mannosidosis 22028 Furthermore, in the brain homogenates of treated mice, some alpha-mannosidase activity was observed. In the alpha-mannosidosis mice, the integrity of the BBB was preserved. Intravenously administrated Evans blue did not cross the
alpha-mannosidosis 22758 [[59]]. The study was performed using low phosphorylated human recombinant alpha-mannosidase (rhLAMAN) in alpha-mannosidosis mice. Low phosphorylation content was shown to correlate with an increased half-life of recombinant
alpha-mannosidosis 23910 immunological response to the recombinant enzyme was associated with high mortality precluding long-term ERT in alpha-mannosidosis mice. Other studies suggest that lysosomal enzymes may cross the BBB in animal models with Krabbe disease
alpha-mannosidosis 24702 enzyme is rapidly reduced. Recently, to overcome the immunological problems associated with ERT in alpha-mannosidosis mice, an immune-tolerant mouse model of alpha-mannosidosis was generated [[66]]. This mouse model allowed
alpha-mannosidosis 24761 immunological problems associated with ERT in alpha-mannosidosis mice, an immune-tolerant mouse model of alpha-mannosidosis was generated [[66]]. This mouse model allowed for an evaluation of the effect of high-dose long-term
alpha-mannosidosis 25635 that can benefit from long-term ERT. To this end, ERT was initiated in 2-month-old immune-tolerant alpha-mannosidosis mice and continued for 9 months. During the course of treatment, mice were trained in the Morris water
alpha-mannosidosis 26153 (30 weeks+) treatment. Long-term treatment substantially improved the spatial-cognitive abilities of alpha-mannosidosis mice, whereas the effects of mid-term treatment were more modest. Detailed analyses of spatial memory
alpha-mannosidosis 27609 overall data of this study indicates that ERT with rhLAMAN is safe and may be used for the therapy of alpha-mannosidosis . The latest result on the ERT for alpha-mannosidosis comes from a Phase III study [[69]]. In this study,
alpha-mannosidosis 27662 rhLAMAN is safe and may be used for the therapy of alpha-mannosidosis. The latest result on the ERT for alpha-mannosidosis comes from a Phase III study [[69]]. In this study, 14 adult patients [mean age 24.6 ± 5.3 years at
alpha-mannosidosis 29790 there are no studies addressing the possibility of using pharmacological chaperons for the therapy of alpha-mannosidosis . Pharmacological chaperons therapy (PCT) might become an alternative to ERT for alpha-mannosidosis in
alpha-mannosidosis 29889 alpha-mannosidosis. Pharmacological chaperons therapy (PCT) might become an alternative to ERT for alpha-mannosidosis in the near future, as has already observed for Fabry disease [[71]]. Pharmacological chaperons selectively
leukodystrophy 13510 diseases with associated neuronal dysfunction, such as Hurler syndrome and cerebral X-linked adreno leukodystrophy [[45]]. In bone marrow transplantation, normal donor stem cells differentiate to different lineages
lysosomal storage disease 1045 patients have been identified and in part characterized at the biochemical level. Similarly to other lysosomal storage disease s, there is no relationship between genotype and phenotype in alpha-mannosidosis. Enzyme replacement
lysosomal storage disease 1227 phenotype in alpha-mannosidosis. Enzyme replacement therapy is at the moment the most effective therapy for lysosomal storage disease , including alpha-mannosidosis. In this review, the genetic of alpha-mannosidosis has been described
lysosomal storage disease 4076 (DEAE-cellulose) [[4]]. The A and B forms are the product of a single gene (MAN2B1), as demonstrated in the lysosomal storage disease alpha-mannosidosis (MIM 248500) in which both A and B are lacking [[5]]. This enzyme has been characterized

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