Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

Hampe, Christiane S.; Wesley, Jacob; Lund, Troy C.; Orchard, Paul J.; Polgreen, Lynda E.; Eisengart, Julie B.; McLoon, Linda K.; Cüreoğlu, Sebahattin; Schachern, Patricia A.; McIvor, R. Scott

doi:10.3390/biom11020189

Cited by 49 publications

(47 citation statements)

References 217 publications

(143 reference statements)

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“…For a comprehensive discussion of current and exploratory treatments for MPS I we refer to earlier reviews [188,189].…”

Section: Treatmentmentioning

confidence: 99%

“…NA Improved [207,215,225] Treatment of MPS I consists of ERT in attenuated cases and hematopoietic stem cell transplantation (HSCT) in patients with severe MPS I, where early transplantation can stem many of the CNS manifestations of the disease [188]. Indeed, MPS I was the first metabolic disease to have a successful disease-modifying therapy, e.g., HSCT [226,227].…”

Section: Activity Of Daily Living (Adl)mentioning

confidence: 99%

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Differences in MPS I and MPS II Disease Manifestations

Hampe

Yund

Orchard

et al. 2021

IJMS

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Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

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“…For a comprehensive discussion of current and exploratory treatments for MPS I we refer to earlier reviews [188,189].…”

Section: Treatmentmentioning

confidence: 99%

Section: Activity Of Daily Living (Adl)mentioning

confidence: 99%

Differences in MPS I and MPS II Disease Manifestations

Hampe

Yund

Orchard

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

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“…Improvements in quality of life and lifespan due to early systemic treatment have meant that the management of ocular complications and the preservation of vision has increased importance for patients with MPS [ 1 , 8 ]. While systemic treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains in areas which are not affected by systemic treatments, for example, corneal clouding [ 17 , 20 ].…”

Section: Systemic Therapies and Their Effect On Corneal Cloudingmentioning

confidence: 99%

“…These will be useful to determine the effectiveness of treatments in research settings and in clinical practice. ERT’s effect on corneal clouding is limited and variable [ 20 , 39 ].…”

Section: Systemic Therapies and Their Effect On Corneal Cloudingmentioning

confidence: 99%

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Management of Corneal Clouding in Patients with Mucopolysaccharidosis

McGrath

Ashworth

2021

JCM

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Mucopolysaccharidoses (MPS) are a rare group of lysosomal storage disorders characterized by the accumulation of incompletely degraded glycosaminoglycans (GAGs) in multiple organ systems including the eye. Visual loss occurs in MPS predominantly due to corneal clouding and retinopathy, but the sclera, trabecular meshwork and optic nerve may all be affected. Despite the success of therapies such as enzyme replacement therapy (ERT) and hematopoietic stem-cell transplantation (HSCT) in improving many of the systemic manifestations of MPS, their effect on corneal clouding is minimal. The only current definitive treatment for corneal clouding is corneal transplantation, usually in the form of a penetrating keratoplasty or a deep anterior lamellar keratoplasty. This article aims to provide an overview of corneal clouding, its current clinical and surgical management, and significant research progress.

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18‐year follow‐up of enzyme‐replacement therapy in two siblings with attenuated mucopolysaccharidosis I

Pjetraj

Santoro

Sgattoni

et al. 2022

American J of Med Genetics Pt A

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Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α‐L‐iduronidase and characterized by a progressive course with multisystem involvement. Clinically, MPS I is divided into two forms: (1) severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement; (2) attenuated (Hurler/Scheie and Scheie syndromes), which displays a slower progression and absent to mild nervous system involvement. The specific treatment for attenuated MPS I consists of enzyme‐replacement therapy with laronidase (human recombinant α‐L‐iduronidase, Aldurazyme). We present updated data after 18 years of laronidase treatment in two siblings affected by the attenuated form of MPS I who started therapy at 5 months and 5 years of age, respectively. Clinical and laboratory data of the siblings show that long‐term enzyme replacement therapy may improve/stabilize many symptoms already present at the time of the diagnosis and reduce the disease progression. This study confirms that early diagnosis and early initiation of enzyme‐replacement therapy are essential to modify positively the natural history of the attenuated form of MPS I.

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Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement

Cited by 49 publications

References 217 publications

Differences in MPS I and MPS II Disease Manifestations

Differences in MPS I and MPS II Disease Manifestations

Management of Corneal Clouding in Patients with Mucopolysaccharidosis

18‐year follow‐up of enzyme‐replacement therapy in two siblings with attenuated mucopolysaccharidosis I

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