Changes in hair morphology of mucopolysaccharidosis I patients treated with recombinant human α‐<scp>L</scp>‐iduronidase (laronidase, Aldurazyme)

Kłoska, Anna; Bohdanowicz, J.; Konopa, Grażyna; Tylki-Szymńska, Anna; Jakóbkiewicz‐Banecka, Joanna; Czartoryska, Barbara; Liberek, Anna; Węgrzyn, Alicja; Węgrzyn, Grzegorz

doi:10.1002/ajmg.a.31021

Cited by 21 publications

(27 citation statements)

References 10 publications

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“…SEM analysis of the hair of these patients indicated that, in contrast to the hair shaft of the control group (healthy volunteers), the hair shafts from MPS I patients were abnormal, as concave and convex areas were apparent on the long hair axis, making the hair appear flat in some areas [9]. Interestingly, these abnormal features disappeared during enzyme replacement therapy with recombinant human α-L-iduronidase (laronidase, Aldurazyme), and, after about one year of treatment, a normal hair morphology was evident.…”

Section: Introductionmentioning

confidence: 69%

“…Recently, we have demonstrated abnormal hair structures of MPS I patients [9]. SEM analysis of the hair of these patients indicated that, in contrast to the hair shaft of the control group (healthy volunteers), the hair shafts from MPS I patients were abnormal, as concave and convex areas were apparent on the long hair axis, making the hair appear flat in some areas [9].…”

Section: Introductionmentioning

confidence: 96%

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Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses

et al. 2007

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Mucopolysaccharidoses (MPS) are a group of inherited, progressive, metabolic diseases, caused by the deficiency of one of the enzymes involved in the degradation of glycosaminoglycans (GAGs). The disease is usually fatal, with the life span of most untreated MPS patients being between one and two decades. In this report, on the basis of scanning electron microscopy (SEM) studies, we demonstrate that, besides the many other symptoms of MPS, there are characteristic abnormalities in the hair morphology of patients suffering from some types of this disease (MPS I, MPS II, MPS IIIA, MPS IIIB), but not from other types (MPS IVA, MPS IVB, MPS VI), where the changes are minor, if any. Different GAGs accumulate in the tissues of patients suffering from the various MPS types, and analysis of the disease types in which severe hair abnormalities occur or not could suggest that the accumulation of heparan sulfate, rather than dermatan sulfate or keratan sufate, may be responsible for the major changes in hair morphology. Considerable abnormalities in hair morphology occur in patients suffering from MPS I, MPS II, MPS IIIA, and MPS IIIB, but not in patients suffering from MPS IVA, MPS IVB, and MPS VI; this feature might potentially be used as an additional test for the assessment of the efficacy of treatments for MPS patients (types I, II, IIIA, and IIIB).

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Section: Introductionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 96%

Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses

et al. 2007

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“…This treatment, in which no adverse effects were noted, resulted in a statistically significant improvement in all tested parameters (Piotrowska et al 2008). Particularly, urinary GAG levels were reduced, hair morphology (which may be a useful parameter in monitoring efficacy of treatment of patients suffering from various MPS types; Kloska et al 2005;Wegrzyn et al 2007;Malinowska et al 2008) improved, and patients got higher scores in the psychological test by which cognitive functions could be assessed (Piotrowska et al 2008). Nevertheless, one must note that the positive changes were not dramatic, occurred in only a fraction of patients, and the measured parameters did not reach values estimated for healthy children.…”

Section: Efficacy Of Srt In In Vitro Studies Experiments With Animalmentioning

confidence: 82%

Putative Biological Mechanisms of Efficiency of Substrate Reduction Therapies for Mucopolysaccharidoses

Banecka-Majkutewicz

Jakóbkiewicz‐Banecka

Gabig-Cimińska

et al. 2012

Arch. Immunol. Ther. Exp.

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Mucopolysaccharidoses (MPS) are inherited metabolic diseases caused by mutations in genes coding for lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Dysfunction of any of these enzymes results in the accumulation of GAGs, which leads to severe clinical symptoms and significantly shortened life span. Several kinds of therapies have been proposed to treat MPS, including bone marrow or stem cell transplantation, enzyme replacement therapy, and gene therapy. Another option is substrate reduction therapy (SRT), in which synthesis of GAGs is inhibited. Recent studies employing in vitro and animal models suggested that this therapy may be efficient in decreasing levels of GAGs in MPS cells, including those bearing two null alleles of the affected gene. Results of behavioral tests in animals as well as some preliminary clinical observations with pediatric patients corroborated the suggestions about possible efficacy of SRT in MPS treatment, including brain functions. Efficient reduction of GAG levels in MPS cells homozygous for null mutations may be intriguing in the commonly accepted scheme of SRT mode of action. In this paper, we propose an explanation of this phenomenon, based on already known facts. Thus, we suggest that SRT may lead to reduction of GAG levels in MPS cells due to inhibition of efficiency of GAG synthesis combined with (a) any readthrough of the stop codon, (b) dilution of already accumulated GAGs due to cell growth followed by cell divisions, and (c) action of endoglycosidases degrading GAGs, e.g., heparanase, in combination with functional GAG-specific hydrolases.

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“…Because of the suggested mechanism of action of genistein (an isoflavone), we propose to call this type of treatment 'gene expression-targeted isoflavone therapy' (GET IT). Although ERT may be potentially more efficient in treatment of at least some somatic tissues of MPS patients, 6,24,25 an advantage of GET IT is that genistein is able to cross the blood -brain barrier. 26 Therefore, this might be a chance for treatment of neurological symptoms of MPS, which is currently not possible.…”

Section: Discussionmentioning

confidence: 99%

Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses

et al. 2006

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Mucopolysaccharidoses (MPS) are inherited, severe, progressive, metabolic disorders caused by deficiencies in different enzymes involved in degradation of glycosaminoglycans (GAGs). Although enzyme replacement therapy (ERT) has recently been available for MPS type I, and clinical trials have been performed in ERT for MPS II and MPS VI, there is little chance that this kind of treatment may be effective for neurodegenerative forms of MPS (due to inefficient delivery of enzymes to central nervous system through the blood -brain barrier), hence currently there is no effective therapy available for them. Therefore, we aim to develop an alternative therapy for these diseases. We found that genistein (4 0 ,5, 7-trihydroxyisoflavone or 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) inhibits synthesis of GAGs considerably in cultures of fibroblasts of MPS patients (types I, II, IIIA and IIIB were tested). Prolonged cultivation of these cells in the presence of genistein resulted in reduction of GAG accumulation and normalization of cells as estimated by biochemical tests and electron microscopic analysis, respectively. As genistein inhibits kinase activity of epidermal growth factor receptor, which is required for full expression of genes coding for enzymes involved in GAG production, we propose to consider a substrate reduction therapy for MPS, which is referred to as 'gene expression-targeted isoflavone therapy'.

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Changes in hair morphology of mucopolysaccharidosis I patients treated with recombinant human α‐L‐iduronidase (laronidase, Aldurazyme)

Cited by 21 publications

References 10 publications

Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses

Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses

Putative Biological Mechanisms of Efficiency of Substrate Reduction Therapies for Mucopolysaccharidoses

Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses

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