Enzyme replacement therapy with laronidase (Aldurazyme<sup>®</sup>
) for treating mucopolysaccharidosis type I

Jameson, Elisabeth; Jones, Simon A.; Remmington, Tracey

doi:10.1002/14651858.cd009354.pub4

Cited by 42 publications

(32 citation statements)

References 19 publications

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“…1 Among the other approaches, enzyme replacement therapy with Laronidase (recombinant human IDUA; Aldurazyme (Genzyme Corporation) is mainly used to treat MPSI in United States, Europe, and many other countries. 2 MPSI is considered to be one of the most commonly lysosomal storage disorders in different populations with a mean incidence of 1:100 000-1:150 000 newborns. 3,4 The IDUA gene is located on chromosome 4p16.3 and covers nearly 19 kb.…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Taghikhani

Khatami

Abdi

et al. 2019

Clinical Laboratory Analysis

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BackgroundMucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused by a deficiency of α‐l‐iduronidase (IDUA) encoded by the IDUA gene. We examined the mutation spectrum of the IDUA gene to explain the clinical, biochemical, and molecular features in 21 Iranian patients with MPSI.MethodsSanger sequencing was used to measure the IDUA gene sequence in the coding region and exon‐intron boundaries. We recorded the clinical findings of studied patients at the first diagnosis of disease and then during the treatment and follow‐up.ResultsFive different missense disease‐causing mutations were determined in our patient groups, indicating 90.48% of detection rate. The most widespread mutation was the p.Y109H, occurring in 15.625% of all alleles, which was reported for the first time in our study. Other frequent mutations were as follows: p.Ser157Pro (12.5%), p.Gly84Arg (12.5%), p.Asp257His (9.375%), and p.Asp301Glu (9.375%). Three ones of them were new missense mutations: p.Ser157Pro, p.Asp257His, and p.Asp301Glu.DiscussionThe results of this study explain the different spectrum of IDUA gene mutations in our patients with MPSI. We introduced here 32 different variants including four new variants: p.Y109H (15.625%), p.S157P (12.5%), p.D257H (9.375%), and p.D301E (9.375%). In this series, there was no relationship between the happening of clinical features and genotype variations and biochemical findings.

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Section: Introductionmentioning

confidence: 99%

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Taghikhani

Khatami

Abdi

et al. 2019

Clinical Laboratory Analysis

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“…ERT with human recombinant laronidase (a polymorphic form of human α-L-iduronidase) is the most diffuse treatment for attenuated MPS I [10, 11] and its safety and efficacy have been proven over the years [12]. It is not recommended for the severe Hurler form because the enzyme is unable to cross the blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Open issues in Mucopolysaccharidosis type I-Hurler

Parini

Deodato

Rocco

et al. 2017

Orphanet J Rare Dis

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Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary followup with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H.

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“…Enzyme replacement therapy with a recombinant human alpha-L-iduronidase (laronidase) is an important treatment option for these patients. Such therapy improves lung function, walking ability, urine GAG excretion, hepatomegaly, and sleep apnea, but not CNS manifestations because the blood-brain barrier effectively blocks treatment by preventing enzyme entry [1, 2]. …”

Section: Discussionmentioning

confidence: 99%

“…The life expectancy of patients with MPS I is less than 10 years. Enzyme replacement therapy with laronidase (a recombinant human alpha-L-iduronidase, rhIDU) has been shown to improve organ function but not produce neurological benefits owing to its lack of blood-brain barrier (BBB) penetration [1, 2]. …”

Section: Introductionmentioning

confidence: 99%

Transcranial pulsed ultrasound facilitates brain uptake of laronidase in enzyme replacement therapy for Mucopolysaccharidosis type I disease

Hsu

Liu

Lin

et al. 2017

Orphanet J Rare Dis

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BackgroundMucopolysaccharidosis type I (MPS I) is a debilitating hereditary disease characterized by alpha-L-iduronidase (IDUA) deficiency and consequent inability to degrade glycosaminoglycans. The pathological accumulation of glycosaminoglycans systemically results in severe mental retardation and multiple organ dysfunction. Enzyme replacement therapy with recombinant human alpha-L-iduronidase (rhIDU) improves the function of some organs but not neurological deficits owing to its exclusion from the brain by the blood-brain barrier (BBB).MethodsWe divided MPS I mice into control group, enzyme replacement group with rhIDU 2.9 mg/kg injection, enzyme replacement with one-spot ultrasound treatment group, and enzyme replacement with two-spot ultrasound treatment group, and compare treatment effectiveness between groups. All ultrasound treatments were applied on left side brain. Evans blue was used to simulate the distribution of rhIDU in the brain.ResultsTranscranial pulsed weakly focused ultrasound combined with microbubbles facilitates brain rhIDU delivery in MPS I mice receiving systemic enzyme replacement therapy. With intravenously injected rhIDU 2.9 mg/kg, the IDUA enzyme activity on the ultrasound treated side of the cerebral hemisphere raised to 7.81-fold that on the untreated side and to 75.84% of its normal value. Evans blue simulation showed the distribution of the delivered drug was extensive, involving a large volume of the treated cerebral hemisphere. Two-spot ultrasound treatment scheme is more efficient for brain rhIDU delivery than one-spot ultrasound treatment scheme.ConclusionsTranscranial pulsed weakly focused ultrasound can open BBB extensively and facilitates brain rhIDU delivery. This novel technology may provide a new MPS I treatment strategy.

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Enzyme replacement therapy with laronidase (Aldurazyme^® ) for treating mucopolysaccharidosis type I

Cited by 42 publications

References 19 publications

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Open issues in Mucopolysaccharidosis type I-Hurler

Transcranial pulsed ultrasound facilitates brain uptake of laronidase in enzyme replacement therapy for Mucopolysaccharidosis type I disease

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Enzyme replacement therapy with laronidase (Aldurazyme® ) for treating mucopolysaccharidosis type I

Cited by 42 publications

References 19 publications

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Open issues in Mucopolysaccharidosis type I-Hurler

Transcranial pulsed ultrasound facilitates brain uptake of laronidase in enzyme replacement therapy for Mucopolysaccharidosis type I disease

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Product

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Enzyme replacement therapy with laronidase (Aldurazyme^® ) for treating mucopolysaccharidosis type I