Selective Screening for Lysosomal Storage Diseases with Dried Blood Spots Collected on Filter Paper in 4,700 High-Risk Colombian Subjects

Uribe, Alfredo; Giugliani, Roberto

doi:10.1007/8904_2013_229

Cited by 26 publications

(36 citation statements)

References 33 publications

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“…The prevalence of males with Fabry disease ranges from 1:17,000 to 1:117,000 in the Caucasian population 4, 5. Recent newborn screening studies have, however, indicated a much higher incidence of this disorder because patients with later onset and milder forms of Fabry disease are found even more commonly than expected, suggesting that they are possibly underdiagnosed 6, 7, 8, 9, 10, 11, 12, 13…”

Section: Introductionmentioning

confidence: 99%

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34 + Cells for Correction of Fabry Disease

Huang

Khan

et al. 2017

Molecular Therapy - Methods & Clinical Development

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Fabry disease is a rare lysosomal storage disorder (LSD). We designed multiple recombinant lentivirus vectors (LVs) and tested their ability to engineer expression of human α-galactosidase A (α-gal A) in transduced Fabry patient CD34+ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34+ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34+ hematopoietic cells. We successfully transduced Fabry patient CD34+ hematopoietic cells with “near-clinical grade” LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34+ hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF) mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA) to Health Canada and opening of a “first-in-the-world” gene therapy trial for Fabry disease.

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Section: Introductionmentioning

confidence: 99%

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34 + Cells for Correction of Fabry Disease

Huang

Khan

et al. 2017

Molecular Therapy - Methods & Clinical Development

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“…For dried blood spot (DBS) samples, we evaluated the same group of patients, but the DBS activity values were compared with their reported reference values. 11…”

Section: Methodsmentioning

confidence: 99%

“…Both methods for evaluation of BGal used the same fluorogenic substrate (4-methylumbelliferyl-β-D-galactoside) and incubation buffer (citrate-phosphate). The DBS samples were analyzed by duplicate according to the method described by Uribe and Giugliani, 11 and the enzymatic activities were expressed as nanomol of substrate hydrolyzed per milliliter of sample per hour (nmol/mL/h). Here milliliters are calculated in accordance to what Uribe and Giugliani 11 described for DBS punches of 1.2 mm.…”

Section: Methodsmentioning

confidence: 99%

“…The DBS samples were analyzed by duplicate according to the method described by Uribe and Giugliani, 11 and the enzymatic activities were expressed as nanomol of substrate hydrolyzed per milliliter of sample per hour (nmol/mL/h). Here milliliters are calculated in accordance to what Uribe and Giugliani 11 described for DBS punches of 1.2 mm. Leukocyte samples were analyzed following the protocol of Shapira 12 by duplicate, and activities are expressed in nanomol of substrate hydrolyzed by milligram of protein per hour (nmol/mg protein/h).…”

Section: Methodsmentioning

confidence: 99%

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β-Galactosidase Deficiency in Colombia

Uribe

Ayala

España

et al. 2015

Journal of Inborn Errors of Metabolism and Screening

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β-Galactosidase (BGal) is the first enzyme involved in the catabolism of sphingolipids. Two pathologies have been directly associated with its deficiency: GM1 gangliosidosis and Morquio B. Morquio B is among the rarest types of mucopolysaccharidosis (MPS). We aim to document the β-galactosidase deficiency in Colombia. We evaluated leukocytes from 1492 healthy Colombian individuals and 923 patients, referred between 2005 and August 2014. Dried blood spot (DBS) samples from the same number of patients were evaluated. β-Galactosidase was measured with 4-methylumbelliferyl-β-d-galactoside. As a control enzyme, the total hexosaminidase activity was also evaluated. We identified 14 patients with GM1 gangliosidosis, 5 patients with Morquio B, and 1 patient with I-cell disease. We could establish a reference value for Bgal in Colombian leukocyte samples. GM1 gangliosidosis is the main pathology associated with a direct deficiency of BGal. The high number of patients found with MPS IVB indicates that there are patients who could be misdiagnosed due to an unawareness of the disease.

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“…In such context, development of high-throughput methods for enzyme analysis using DBSs [49] or the analysis of GAG species in urine samples [50] made feasible the possibility of newborn screening programs for MPS diseases, in particular, for MPS I, II and VI where there is possibility of therapy with bone marrow transplant and/or ERT. At the moment, some pilot programs have been developed that probably will have great impact in the current management of MPS patients since early therapeutic strategies could be offered for such patients [51,52].…”

Section: Expert Opinionmentioning

confidence: 99%

Evaluation of galsulfase for the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Lourenço

Giugliani

2014

Expert Opinion on Orphan Drugs

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Introduction: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive lysosomal storage disorder caused by a deficiency in the lysosomal enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B), leading to an accumulation of glycosaminoglycans within lysosomes. MPS VI patients experience a progressive, chronic and multisystemic disease that causes not only significant morbidity but also early mortality. Areas covered: Galsulfase, a recombinant human N-acetylgalactosamine 4-sulfatase, rhASB (Naglazyme Ò), is produced by recombinant DNA technology in a CHO-derived cell line, and was approved in the US (2005) and the EU (2006) for use in MPS VI patients. The authors examine the published pharmacokinetic, safety and efficacy data from the Phase I/II, Phase III, Phase III extension, post-marketing surveillance studies of galsulfase, published case reports and cohort of patients treated with rhASB. Expert opinion: Galsulfase is generally well tolerated, having an acceptable safety profile. Few infusion reactions have occurred during administration of galsulfase, being generally mild-to-moderate in severity. Improvements in 12-minute walk test, nearly significant improvement in 3-min stair climb and significant reduction in urinary GAG levels were demonstrated in the 24-week, randomized, double-blind Phase III trial that led to the approval of the drug. As in other lysosomal storage diseases, the antibody response to enzyme replacement therapy can differ greatly between patients and may to some extent relate to the genotype. Nevertheless, antibody formation seems to have little impact on clinical outcome in MPS VI patients treated with galsulfase.

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Selective Screening for Lysosomal Storage Diseases with Dried Blood Spots Collected on Filter Paper in 4,700 High-Risk Colombian Subjects

Cited by 26 publications

References 33 publications

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34 + Cells for Correction of Fabry Disease

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34 + Cells for Correction of Fabry Disease

β-Galactosidase Deficiency in Colombia

Evaluation of galsulfase for the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

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