Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10year combined experience of 2 centres

Ghosh, Arunabha; Miller, Weston P.; Orchard, Paul J.; Jones, Simon A.; Mercer, Jean; Church, Heather J.; Tylee, Karen; Lund, Troy C.; Bigger, Brian; Tolar, Jakub; Wynn, Robert

doi:10.1016/j.ymgme.2016.01.011

Cited by 54 publications

(61 citation statements)

References 17 publications

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“…This was accompanied by an improvement in visual acuity. The patient also had been treated with ERT before HSCT from the age of 12 months (now standard management) 12 and his biomarkers demonstrated markedly superior values to other patients (Table 1). …”

Section: Corneal Clouding and Com Scorementioning

confidence: 99%

Objective Quantification of Changes in Corneal Clouding Over Time in Patients With Mucopolysaccharidosis

Javed

Aslam

Jones

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Javed A, Aslam T, Jones SA, Ashworth J. Objective quantification of changes in corneal clouding over time in patients with mucopolysaccharidosis. Invest Ophthalmol Vis Sci. 2017;58:954-958. DOI:10.1167/ iovs.16-20647 PURPOSE. We determine objective changes in corneal opacification levels over time in patients with mucopolysaccharidoses (MPS) treated with enzyme replacement therapy or hematopoietic stem cell transplant. A prospective cohort study was done of 9 patients with MPS I (Hurler) or VI (Maroteaux-Lamy).METHODS. Quantification of corneal clouding using the Iris camera and full ophthalmic examination, including subjective assessment of corneal clouding, was done in 2011 and repeated in 2015/2016. Patients also had assessment of biomarkers, including dermatan sulfate/chondroitin sulfate (DS/CS) ratio. Change in corneal opacification were measured by Iris camera corneal opacification measure (COM) score during a mean of 60 months followup. RESULTS.A total of 5/17 (29%) eyes had a deterioration in COM score, indicating increased corneal clouding. There was no significant change in COM score in 10/17 (59%) patient eyes. One patient (2/17 eyes) demonstrated significant improvement in corneal clarity and this was associated with improved biomarker levels.CONCLUSIONS. Assessment of COM scores using the Iris camera are an objective means of monitoring corneal opacification over time in patients with MPS. Corneal opacification may potentially be reversed with intensive treatment demonstrated by impact on biomarkers.Keywords: mucopolysaccharidoses, paediatric ophthalmology, metabolic medicine T he mucopolysaccharidoses (MPS) are a group of rare metabolic diseases characterized by defects of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Glycosaminoglycan deposition in multiple tissues and organs results in a wide range of systemic manifestations, including dysmorphic facial features, vision and hearing impairment, cardiorespiratory problems, joint and bone diseases, neurologic problems, and intellectual impairment. Corneal opacification is an early clinical feature in several of the MPS subtypes (MPSI Hurler and Hurler-Scheie, MPSIVA Morquio, MPSVI Maroteaux-Lamy, MPSVII Sly), and can result in significant visual impairment.1 In addition, complications, such as retinopathy, glaucoma, and optic neuropathy, may contribute to visual loss in patients with MPS. Current treatment options for MPS include enzyme replacement therapy (ERT), which is available for MPS I, II, IVA, and VI; and hematopoietic stem cell transplantation (HSCT), which is useful for selected patients with MPS types I and VI.1,2 The untreated clinical course of corneal clouding in MPS is thought to be one of gradual deterioration, but the extent and speed of deterioration have not been documented. Enzyme replacement therapy is known to be effective in improving the systemic manifestations of MPS in types I, II, IVA, and VI by improving respiratory function and stamina, and improving quality of life.2...

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Section: Corneal Clouding and Com Scorementioning

confidence: 99%

Objective Quantification of Changes in Corneal Clouding Over Time in Patients With Mucopolysaccharidosis

Javed

Aslam

Jones

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Notably, ERT was reported as being very effective in reverting cardiomyopathy and severe heart failure during a period of a few months in a number of Hurler patients who later underwent HSCT [42, 43]. Furthermore, HSCT attenuated the formation of neutralizing allo-antibodies developing upon ERT [44], reinforcing the strength of a strategy based on concurrent ERT and HSCT in the same treatment protocol [17]. …”

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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“…[8][9][10][11][12][13] Laronidase has also been found to be useful in the peritransplant period for patients with severe MPS I. 4,14 The use of ERT in the peritransplant period has been shown to be safe and has led to clinical improvements particularly in patients with significant cardiopulmonary disease before transplantation. In addition, ERT before transplantation has been reported to alleviate symptoms that may have influenced the conditioning regime or candidacy for transplantation of some patients.…”

mentioning

confidence: 99%

“…In addition, ERT before transplantation has been reported to alleviate symptoms that may have influenced the conditioning regime or candidacy for transplantation of some patients. 14 Because MPS I is a progressive disorder, the success of both HSCT and ERT depends on early initiation of treatment. Therefore, early identification of patients is critical.…”

mentioning

confidence: 99%

Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management

Clarke

Atherton

Burton

et al. 2017

The Journal of Pediatrics

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Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10year combined experience of 2 centres

Cited by 54 publications

References 17 publications

Objective Quantification of Changes in Corneal Clouding Over Time in Patients With Mucopolysaccharidosis

Objective Quantification of Changes in Corneal Clouding Over Time in Patients With Mucopolysaccharidosis

Open issues in Mucopolysaccharidosis type I-Hurler

Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management

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