Systemic therapies for mucopolysaccharidosis: ocular changes following haematopoietic stem cell transplantation or enzyme replacement therapy – a review

Abstract

The management of mucopolysaccharidosis (MPS) is focused on the multi-organ, sometimes lifethreatening, clinical manifestations that occur over time. In the past, the limited, symptom-based treatment options led physicians to adopt a palliative approach towards individual disease-associated complications. The availability of systemic treatments such as haematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) has created a better prognosis for MPS patients, particularly when initiated early in life. As part of an integrated management approach, these therapies could be valuable in managing the ocular features that are present in many children with MPS. HSCT has been shown to stabilize or improve corneal clouding and optic nerve oedema for the majority of patients. Retinal degeneration, in contrast, seems not to be permanently arrested. ERT was more recently introduced and has therefore been less well examined than HSCT; with respect to ocular problems in MPS, the majority of reports indicate stabilization of corneal clouding or visual acuity. However, controversy remains about its effect on other ocular pathologies. Despite the lack of consistent ophthalmic improvement for all patients, both treatment modalities deserve consideration, because even reducing MPS-related eye disease progression is worthwhile.

Variability in the ocular phenotype in mucopolysaccharidosis

“…No such relationship has been shown between ERT and ocular phenotype. This may be related to the fact that ERT is unable to cross the blood brain barrier 10. Treatments such as substrate reduction therapy and gene therapy are currently undergoing clinical trails in MPS 5 11…”

Hornhaut-Schlüsselbefunde im Kindesalter als Hinweis für therapierbare systemische Stoffwechselerkrankungen

“…Mucopolysaccharidosen (MPS) sind meist autosomal-rezessiv vererbte Erkrankungen (Ausnahme: MPS II-Hunter X-chromosomal rezessiv), bei denen Enzymdefekte zu einer intrazellulären lysosomalen Speicherung der Glykosaminoglykane in unterschiedlichen Organen führen [19]. …”

“…Die Möglichkeit der systemischen Therapie bei einzelnen Formen von MPS, wie Stammzellentransplantation oder Enzymtherapie, hat die Prognose dieser schweren Krankeitsbilder verbessert, insbesondere, wenn mit der Behandlung möglichst in einem frü-hen Stadium begonnen wird [19]. Für die Behandlung der MPS I-H wurde das Enzympräparat Aldurazyme R im Jahre 2003 in Europa und USA zugelassen [20].…”

Diagnosis and management of ophthalmological features in patients with mucopolysaccharidosis

“…Indeed, HSCT has been reported to reduce but not fully eliminate corneal clouding,15 29 34 to resolve optic nerve oedema15 29 and to improve ERG results 29 62. However, retinal degeneration can progress despite engraftment29 and visual function may remain compromised 34 62.…”

“…Clinically meaningful and sustained improvements in functional capacity and other systemic signs have been observed with ERT in phase III studies 67–72. With respect to ocular manifestations, stability or improvement of corneal clouding and visual acuity was apparently found in some patients, but controversy about other ocular pathologies such as optic disc changes remains 35 36 62 69 71 73–75. More assessments are necessary to provide a clear-cut picture of the effects of ERT, and its combination with HSCT, on the course of ocular changes 4.…”