Enzymatic replacement therapy for Hunter disease: Up to 9years experience with 17 patients

Abstract

Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood–brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m2 decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood–brain barrier, might in the future improve the MPS II outcome.

Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings

“…Over 90% of patients with MPS IVA present ENT complications at an early age, even while being treated with ERT [44][45][46]. In the current study, considering both siblings' findings, it appears that P1's clinical course is consistent with the literature.…”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…Some of these studies are the phase III extension studies and involve the same patients previously enrolled in the Phase III trials [36][37][38][39]71,96,114]. The others are mostly observational studies conducted in a single center on a limited number of cases, or studies performed on data extracted from disease registries [29,34,37,[40][41][42][43][44][47][48][49][50][51][52]70,74,77,84,85,97,116]. Disease registries are a helpful tool to collect data on rare diseases and there is now a huge number of disease registries available for many rare diseases.…”

“…Total urine GAGs concentrations have been used in the Phase II/III trials as markers of the biochemical efficacy of ERT [17][18][19]21,22,30,31,33] and their level can be correlated with the different severity of phenotypes [118,119]. Their decrease is dramatic in the first 6-12 months of treatment and is sustained over the years tending to normalize in almost all patients [29,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]. However, blood and urine dermatan sulfate (DS) and heparan sulfate (HS) derived disaccharides, that are considered more suitable biomarkers for MPS I and II [120][121][122], were persistently elevated in long term ERT-treated MPS I and MPS II patients, and blood mono-and di-sulfated keratan sulfate were elevated in MPS IVA patients on ERT [122,123].…”

“…Most long-term observational studies confirm a progressive reduction of spleen and liver size with a tendency to normalization [36,38,[40][41][42][43]45,46,[48][49][50][51]59,60,85]. Only some patients are reported with spleen and/or liver size stabilization [42,50,60].…”

Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)

“…Treatment before six years old provides the positive effects of somatic improvement [28,115]. This method of treatment has been available since 2006, although guidelines for use vary between nations.…”