2026-08-09 | The IDS Gene Variant c.851C>T, p.P284L: More Evidence Against its Role as a Pathogenic Mutation in Mucopolysaccharidosis Type II

The Data of research The IDS Gene Variant c.851C>T, p.P284L: More Evidence Against its Role as a Pathogenic Mutation in Mucopolysaccharidosis Type II

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2026-07-30 | Treatment outcomes maintained in Hunter syndrome patients: a case series on switching from idursulfase to idursulfase beta in Belarus.

Hunter syndrome (Mucopolysaccharidosis type II, MPS II) is a rare X-linked lysosomal storage disorder caused by iduronate-2-sulfatase deficiency, leading to glycosaminoglycan accumulation. Enzyme replacement therapy (ERT) with idursulfase is a standard treatment, although supply shortages may disrupt continuity of care. This retrospective case series describes clinical and biochemical outcomes in seven patients with Hunter syndrome in Belarus who were switched from idursulfase (Elaprase®) to idursulfase beta (Hunterase®). Patients were evaluated before and after the switch using urinary GAG levels, 6-minute walking test (6MWT), liver and spleen size, and safety parameters. Following the transition, patients maintained or improved clinical outcomes, with continued reductions in urinary GAG levels, stable or improved 6MWT performance, and further decreases in organ enlargement. No new safety concerns were identified. These findings suggest that switching to idursulfase beta may preserve therapeutic benefits and support treatment continuity in real-world settings.

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2026-07-21 | New Paradigms in Management of Central Nervous System Damage in Patients with Hunter Syndrome

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a progressive lysosomal storage disease with X-linked recessive inheritance. This disease is caused by pathogenic or probably pathogenic variants in the IDS gene encoding iduronate 2-sulfatase. This enzyme insufficiency leads to glycosaminoglycans accumulation in cells of various organs and tissues, which underlies the multisystem lesion. There is neuropathic form of MPS II with progressive central nervous system (CNS) damage and behavioral disorders, and milder form without any intellectual disorders. There are methods of effective pathogenetic therapy for this disease, however, they do not affect CNS manifestations. Thus, there is topical issue in management of neuropathic MPS II forms on transporting enzyme-replacement medications through the blood-brain barrier (BBB). Development of pabinafusp alfa (JR-141), innovative drug penetrating the BBB via transcytosis mediated by the transferrin receptor, became one of the approaches to solve this problem. This publication provides the literature review on the pabinafusp alfa administration for management of neuropathic MPS II forms focusing its efficacy and safety.

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2026-07-09 | Sustained clinical benefit of idursulfase beta in mucopolysaccharidosis II: two-year experience from a phase 3 extension study including patients switched from idursulfase.

Long-term safety and efficacy data on enzyme replacement therapy, particularly switching between recombinant iduronate-2-sulfatase formulations, remain limited in mucopolysaccharidosis II (MPS II). This open-label extension study included male patients with MPS II who completed a 52-week, phase 3 trial and either continued idursulfase beta (maintenance group, n = 22) or switched from idursulfase (switch group, n = 6). Participants received weekly intravenous idursulfase beta (0.5 mg/kg) for an additional 52 weeks. Safety, immunogenicity, six-minute walk test (6-MWT), and urinary glycosaminoglycan (GAG) levels were evaluated longitudinally for two years. Changes over time were analyzed using descriptive statistics and mixed models for repeated measures. Over the two-year treatment period, no new safety signals were identified in both groups. In the maintenance group, the incidence of adverse drug reactions decreased in the second year compared with the first year (from 54.5% to 13.6%); anti-drug antibody positivity peaked within the first six months and subsequently declined, with a low prevalence of neutralizing antibodies (4.5-22.7%). At Month 24, least-square mean changes from baseline demonstrated a 23.1% increase in 6-MWT distance and a 73.1% reduction in urinary total GAG levels in the maintenance group. Patients switching from idursulfase showed comparable safety profiles and sustained functional and biochemical improvements. These results demonstrate that idursulfase beta is safe and efficacious in the long-term management of MPS II. Additionally, switching from idursulfase to idursulfase beta preserved therapeutic efficacy without additional safety or immunogenicity concerns, supporting idursulfase beta as a viable option following prior idursulfase therapy. The study was registered at ClinicalTrials.gov (identifier, NCT07344376 date of registration, 7 January 2026).

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2026-06-22 | Mitochondrial morphology and mtDNA content in fibroblasts from patients with different types of mucopolysaccharidosis

Mucopolysaccharidosis (MPS) is a group of inherited metabolic diseases, characterized by defects in the degradation of glycosaminoglycans and their accumulation in lysosomes. However, various secondary cellular changes also contribute to the pathomechanism of MPS. Previous studies have reached contradictory conclusions about the changes in mitochondria in MPS, from increased numbers of mitochondria to impaired activities of some mitochondrial respiratory chain enzymes to no changes in mitochondrial respiration. In this preliminary, hypothesis-generating study, mitochondrial network morphology and mitochondrial DNA (mtDNA) abundance were investigated in fibroblasts derived from patients suffering from diverse MPS types. Fluorescence microscopy and real-time PCR were used to estimate these parameters, respectively. No significant changes in the mitochondrial network morphology were detected in MPS fibroblasts relative to control cells. Decreased levels of mtDNA relative to nuclear DNA levels were evident in some (I, II, IIIA, IIID, and VI) but not all MPS types compared to control fibroblasts. The results of this study suggest that there are some, although perhaps not dramatic, impairments of mitochondrial functions in some MPS types; however, they do not provide direct evidence of mitochondrial dysfunction. Therefore, these findings should be interpreted as descriptive and exploratory, highlighting the need for further functional and mechanistic studies.

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