Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis

Munoz-Rojas, Maria Veronica; Horovitz, Dafne Dain Gandelman; Jardim, Laura Bannach; Raymundo, Márcia Mocellin; Llerena, Juan Clinton; Magalhães, Tatiana de Sá Carneiro Pacheco de; Vieira, Taiane Alves; Costa, Ronaldo Campelo da; Kakkis, Emil; Giugliani, Roberto

doi:10.1016/j.ymgme.2009.11.008

Cited by 59 publications

(35 citation statements)

References 20 publications

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“…These results were similar to those found in mature immunotolerized MPS-VI cats (14) and support the contention that repeated IT-INJ is a safe and efficacious means of regularly administering enzyme into the CNS in MPS-VI and other lysosomal storage disorders for which development of paresis needs to be prevented (6,7) or in which brain function is impaired (16,(23)(24)(25)28,29).…”

Section: Articlessupporting

confidence: 85%

“…The small, focal, Wallerian-type degeneration observed near the site of IT-INJ in most intrathecally treated cats, irrespective of presence or absence of polysorbate-80, was attributed to mild iatrogenic trauma produced during IT-INJ, as previously reported (14), again highlighting the importance of a good injection technique (14). The lumbar region (L4-L5 space) has been used for IT-INJ of recombinant enzyme in MPS-I and MPS-VI patients (27,28); ultrasound guidance will likely be used to localize the subarachnoid space for precise delivery of enzyme into the CSF. The phenotypic improvements observed in the rhASB-treated MPS-VI cats in this study, such as increased bone length, reduced kyphosis, and improved facial appearance were attributed to the early initiation of weekly IV-ERT, again confirming its efficacy (10,11).…”

Section: Articlesmentioning

confidence: 54%

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Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

et al. 2011

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Section: Articlessupporting

confidence: 85%

Section: Articlesmentioning

confidence: 54%

Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

et al. 2011

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“…22,68 As an alternative to direct enzymes into the brain and reverse neuroimaging features, the application of ERT via intrathecal administration was used in 2 patients with MPS I 73 and VI. 74 Follow-up MR imaging studies showed no worsening of WMA and spinal cord compression in the first patient; yet, intrathecal administration of the enzyme in the second patient led to generalized hypotonia, probably due to reduction of GAG storage and revelation of the instability of the cervical vertebrae. The above data underline the supposition that MR imaging could probably represent a valuable tool in the assessment of the efficacy of various treatment options and could provide reliable markers to estimate neurologic disease burden.…”

Section: Effect Of Therapeutic Regimens In Mr Imaging Findingsmentioning

confidence: 86%

Brain and Spinal MR Imaging Findings in Mucopolysaccharidoses: A Review

Zafeiriou

Batzios

2012

AJNR Am J Neuroradiol

115

105

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SUMMARY: MPS represents a group of rare hereditary disorders characterized by multisystem involvement due to intralysosomal GAG accumulation. Among various tissues, both the central and peripheral nervous system are affected in almost all types of the disease. Thus, brain and spinal MR imaging are valuable tools for the assessment of neurologic involvement, and there is evidence that they might be reliable markers demonstrating disease severity and efficacy of treatment options currently used in patients with MPS. We aimed to review the most prominent MR imaging features of patients with MPS, paying attention to the physiopathologic mechanisms responsible for these alterations. Along with the description of neuroimaging findings, existing data in relation to their correlation with the severity of neurologic involvement is discussed, while another topic of great importance is the effect of various therapeutic regimens in the progression of brain and spinal MR imaging alterations. Finally, recent data concerning MR spectroscopy studies in MPS are also critically discussed. ABBREVIATIONS:ERT ϭ enzyme replacement therapy; GAG ϭ glycosaminoglycan; HSCT ϭ hematopoietic stem cell transplantation; MPS ϭ mucopolysacchari-

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“…Enzyme replacement therapy (ERT) has also been able to stabilize the visceral manifestations of both MPSIH and MPSII, but its lack of ability to cross the blood-brain barrier (BBB) has prevented successful treatment of the neurologic aspects of these diseases through intravenous infusions of enzyme (4,6 ). Recently, the delivery of these enzymes through an intra-thecal route has been explored as a means of improving neurological outcomes (7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

Analysis of Glycosaminoglycans in Cerebrospinal Fluid from Patients with Mucopolysaccharidoses by Isotope-Dilution Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry

et al. 2011

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BACKGROUND New therapies for the treatment of mucopolysaccharidoses that target the brain, including intrathecal enzyme replacement, are being explored. Quantitative analysis of the glycosaminoglycans (GAGs) that accumulate in these disorders is required to assess the disease burden and monitor the effect of therapy in affected patients. Because current methods lack the required limit of quantification and specificity to analyze GAGs in small volumes of cerebrospinal fluid (CSF), we developed a method based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). METHODS Samples of CSF (25 μL) were evaporated to dryness and subjected to methanolysis. The GAGs were degraded to uronic acid-N-acetylhexosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from heparan, dermatan and chondroitin sulfates (HS, DS and CS) were separated by UPLC and analyzed by electrospray ionization MS/MS using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. RESULTS CSF from control pediatric subjects (n = 22) contained <0.38 mg/L HS, 0.26 mg/L DS, and 2.8 mg/L CS, whereas CSF from patients with Hurler syndrome (n = 7) contained concentrations of DS and HS that were at least 6-fold greater than the upper control limits. These concentrations were reduced by 17.5% to 82.5% after allogeneic transplantation and treatment with intrathecal and intravenous enzyme replacement therapy. CONCLUSIONS The method described here has potential value in monitoring patients with mucopolysaccharidoses receiving treatment targeted to the brain.

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Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis

Cited by 59 publications

References 20 publications

Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

Brain and Spinal MR Imaging Findings in Mucopolysaccharidoses: A Review

Analysis of Glycosaminoglycans in Cerebrospinal Fluid from Patients with Mucopolysaccharidoses by Isotope-Dilution Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry

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