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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2026-06-22 | Clinical Outcomes of Ayurvedic Management in Hunter Syndrome: A Case Report

Introduction: Hunter Syndrome, otherwise called Mucopolysaccharidosis Type II, is a rare X- linked Lysosomal Storage disorder, occurring due to the deficiency of Iduronate-2-sulfatase enzyme (I2S). This leads to impaired Glycosaminoglycans catabolism (GAGs), resulting in the pathological accumulation of Heparan sulfate and Dermatan sulfate in multiple tissues and organs. It manifests as a progressive, multisystemic, genetic metabolic disorder. In Ayurveda, Hunter Syndrome is correlated with Sahaja Vyadhi (genetic disease) arising due to genetic defects, manifesting with persistent, impaired metabolism, coarse facies, hirsutism, multiple joint contractures, short stature, hyperactivity, and subnormal cognitive development. Methods: A single case study of a 4-year-old boy with Hunter syndrome was evaluated to analyze the efficacy of ayurvedic therapies on the quality of life. The child was managed with symptomatic treatment and rejuvenation therapy. Oral medicines were targeted for Deepana (appetite stimulant), and Pachana (digestive) to rectify metabolism and to improve cognitive abilities. Procedure-based therapies were targeted to treat physical impairments. Results: After five months of exclusive oral medications and one course of external therapies, the child showed improvement in metabolic activity, cognitive abilities and joint mobility, marking overall well-being and enhanced quality of life. Conclusion: Hunter syndrome is an early onset, progressive disorder, with high morbidity and poor life expectancy, making it a Sahaja Vata Pradhana Tridoshaja Vyadhi. Early diagnosis, genetic counseling, and an integrative approach combining contemporary and traditional therapeutic strategies may reduce mortality and improve long- term health outcomes in affected children.

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