Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future

Taylor, Madeleine; Khan, Shaukat; Stapleton, Molly; Wang, Jianmin; Chen, Jing; Wynn, Robert; Yabe, Hiromasa; Chinen, Yoshiaki; Boelens, Jaap Jan; Mason, Robert W.; Kubaski, Francyne; Horovitz, Dafne Dain Gandelman; Barth, Anneliese Lopes; Serafini, Marta; Bernardo, Maria Ester; Kobayashi, Hironori; Orii, Kenji E.; Suzuki, Yasuyuki; Orii, Tadao; Tomatsu, Shunji

doi:10.1016/j.bbmt.2019.02.012

Cited by 124 publications

(149 citation statements)

References 180 publications

(592 reference statements)

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“…Clinically, MPS IVA patients are characterized by short stature, corneal clouding, hypoplasia of the odontoid process, pectus carinatum, valvular heart disease, mild hepatomegaly, laxity of joints, kyphoscoliosis, and genu valgum without CNS impairment [81][82][83]. Treatment options for MPS IVA patients include non-steroidal anti-inflammatory drugs, antibiotics, oxygen supplementation, surgical procedures to correct orthopedic deformities and tracheal obstructions, ERT, and HSCT [81,82,84]. ERT has showed slight improvement in the 6-min walk test and the reduction of urinary KS [85], as well as an improvement in the maximal voluntary ventilation and performance of daily life activities [86].…”

Section: Mucopolysaccharidosis Type Ivamentioning

confidence: 99%

Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses

Diaz

Castillo

Rodríguez-López

et al. 2019

IJMS

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The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. It this sense, it has been proposed that the use of small molecules, called pharmacological chaperones (PCs), can restore the folding, trafficking, and biological activity of mutated enzymes. PCs have the advantages of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity than enzyme replacement therapy. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

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Section: Mucopolysaccharidosis Type Ivamentioning

confidence: 99%

Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses

Diaz

Castillo

Rodríguez-López

et al. 2019

IJMS

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“…[2][3][4] Treatment for MPSI is available through enzyme replacement therapy and stem cell transplantation. [5][6][7][8][9] It has consequently been suggested that this conditions is amenable to newborn screening (NBS). [5][6][7][8][9] NBS pilot studies have been initiated in the United States as well as other countries.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9] It has consequently been suggested that this conditions is amenable to newborn screening (NBS). [5][6][7][8][9] NBS pilot studies have been initiated in the United States as well as other countries. 2,3 In addition, MPSI was added in 2016 to the recommended universal screening panel in the United States.…”

Section: Introductionmentioning

confidence: 99%

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

et al. 2020

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Purpose Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha‐L‐iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS). Methods We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early‐onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool. Results Every case of early‐onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early‐onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%. Conclusions Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis‐based approach, which was developed for Krabbe disease, can be extended to additional screened disorders.

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“…ERT is routinely and successfully used in patients with several types of MPS [7]. ERT using a recombinant human GUS enzyme, vestronidase alfa, was approved by the FDA and EMA in 2019.…”

Section: Discussionmentioning

confidence: 99%

“…For ERT, a recombinant form of human GUS (vestronidase alpha) has been recently developed and used successfully [5], giving rise to a reduction of urinary GAGs and an improvement of the organomegaly [6]. However, the intravenously injected rhGUS does not cross the blood-brain-barrier and provides no effect on neurological signs, while HSCT can bring the enzyme into the brain via its secretion from donor-derived microglial cells and prevent or slow the neurological deterioration [7]. As learned from other MPS types, HSCT should be performed at an early stage of these diseases in the absence of pre-existing neurological damage.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Follow-up Posthematopoietic Stem Cell Transplantation in a Japanese Patient with Type-VII Mucopolysaccharidosis

et al. 2020

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The effectiveness of hematopoietic stem cell transplantation (HSCT) for type-VII mucopolysaccharidosis (MPS VII, Sly syndrome) remains controversial, although recent studies have shown that it has a clinical impact. In 1998, Yamada et al. reported the first patient with MPS VII, who underwent HSCT at 12 years of age. Here, we report the results of a 22-year follow-up of that patient post-HSCT, who harbored the p.Ala619Val mutation associated with an attenuated phenotype. The purpose of this study was to evaluate changes in physical symptoms, the activity of daily living (ADL), and the intellectual status in the 34-year-old female MPS VII patient post-HSCT, and to prove the long-term effects of HSCT in MPS VII. Twenty-two years after HSCT, the β-glucuronidase activity in leukocytes remained at normal levels, and urinary glycosaminoglycan excretion was reduced and kept within normal levels. At present, she is capable of sustaining simple conversation, and her intellectual level is equivalent to that of a 6-year-old. She can walk alone and climb upstairs by holding onto a handrail, although she feels mild pain in the hip joint. The cervical vertebrae are fused with the occipital bone, causing dizziness and light-headedness when the neck is bent back. Overall, her clinical condition has been stabilized and kept well for long-term post-HSCT, indicating that HSCT is a therapeutic option for MPS VII.

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Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future

Cited by 124 publications

References 180 publications

Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses

Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

Long-Term Follow-up Posthematopoietic Stem Cell Transplantation in a Japanese Patient with Type-VII Mucopolysaccharidosis

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