2026-08-05 | First bone marrow transplantation for mucopolysaccharidosis type I in Vietnam: a case report.

Mucopolysaccharidosis type I (MPS-I) is an inherited lysosomal storage disorder characterized by alpha-L-iduronidase deficiency, leading to progressive multi-organ damage and fatal complications. Early treatment is crucial to improve outcomes, particularly in patients with severe phenotypes. We present the first case of successful allogeneic bone marrow transplantation (BMT) for MPS-I in Vietnam. A 10-month-old girl experienced coarse facial features, congenital dermal melanocytosis spots, kyphoscoliosis developmental delay. Laboratory analyses revealed reduced alpha-L-iduronidase activity and elevated urinary glycosaminoglycans, genetic mutations identified two heterozygous mutations in the IDUA gene, confirmed the diagnosis of MPS-I. At 3 years old, she underwent allogeneic BMT from an HLA-matched sibling donor following conditioning regimen with busulfan, cyclophosphamide, antithymocyte globulin. Neutrophil engraftment was achieved on day +24, and platelet engrafted on day +32. The post-transplant course was complicated by respiratory deterioration requiring 5 days of mechanical ventilation, which was promptly managed and resolved. No graft-versus-host disease occurred. Post-transplant chimerism showed 95.77% donor-derived cells on day +30 and remained stable at 100% from 2 months. The patient demonstrated improvement in clinical symptoms, accompanied by alpha-L-iduronidase activity returned to normal range, urinary glycosaminoglycan levels decreased and remained stable during follow-up. At 12 months, she demonstrated complete immune reconstitution. This case suggests that allogeneic BMT may be a therapeutic approach for patients with MPS-I in resource-limited settings.

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2026-07-04 | Systemic and Orofacial Manifestations of Hurler Syndrome: A Short Communication

Hurler syndrome (mucopolysaccharidosis type I) is a rare autosomal recessive lysosomal storage disorder resulting from deficiency of the enzyme α-L-iduronidase, leading to systemic accumulation of glycosaminoglycans. The disorder manifests early in childhood with progressive multisystem involvement, including characteristic craniofacial features, skeletal abnormalities, cardiopulmonary compromise, and neurological issues. From a dental perspective, patients commonly present with macroglossia, thick lips, delayed tooth eruption, hypoplastic and peg-shaped teeth, gingival hyperplasia, malocclusion, and increased risk of dental caries. These oral findings, combined with airway narrowing, cervical spine instability, and cardiac involvement, pose significant challenges during dental treatment. Diagnosis is based on clinical features, enzyme activity assays, urinary glycosaminoglycan analysis, and molecular genetic testing, with prenatal diagnosis possible. Management requires a multidisciplinary approach involving enzyme replacement therapy, hematopoietic stem cell transplantation, and supportive surgical and rehabilitative care. Dental management emphasizes preventive strategies, early intervention, and careful treatment planning, often necessitating sedation or general anesthesia under strict medical supervision. This short communication aims to highlight the key oral and systemic features of Hurler syndrome and underscores the critical role of dentists in early recognition, prevention, and safe dental management of affected children.

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2026-06-21 | Oral nanoparticle-encapsulated enzyme replacement therapy for mucopolysaccharidosis type I (MPS-I): a proof of concept study.

Mucopolysaccharidosis type I (MPS-I) is a rare, multisystemic lysosomal storage disease (LSD) caused by mutations in the IDUA gene, which encodes the enzyme alpha-L-iduronidase. Current treatments include hematopoietic stem cell transplantation and enzyme replacement therapy (ERT), administered via weekly intravenous infusions. ERT is of limited efficacy owing to its inability to reach critical tissues such as the brain and bone. To address these limitations, this study explores a novel method to improve drug delivery to target organs and simplify administration: oral administration of enzyme encapsulated within nanostructured lipid carriers (NLC). Encapsulation of ERT within NLC enabled effective oral administration. In vitro analysis showed that our NLC formulation was as effective as intravenous ERT in correcting enzyme activity and reducing glycosaminoglycan (GAG) accumulation in fibroblasts from MPS-I patients, when administered periodically. Permeability studies confirmed passage across the intestinal barrier. Proteomic analyses demonstrated normalization of protein expression in energetic pathways related to hexose metabolism, and significant improvements in protein dysregulation in the cytoskeleton, cellular trafficking, lysosomal function, GAG biosynthesis and degradation, and the extracellular matrix. Furthermore, in vivo studies in MPS-I knockout (KO) mice demonstrated biodistribution of NLC-encapsulated enzymes to all tissues affected by the disease, including passage across the blood-brain barrier and access to poorly vascularized bone. These findings suggest that oral administration of ERT via NLC encapsulation represents a significant advancement in MPS-I treatment, enabling drug delivery to previously inaccessible areas. This study opens important avenues of research for future therapeutic strategies targeting LSDs.

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2026-06-13 | Unwrapping the Lysosomal Dysfunction: Clinical Imaging of Hurler’s Multisystem Impact

Hurler's syndrome is a rare lysosomal storage disorder caused by deficiency of lysosomal enzyme α-iduronidase. It follows an autosomal recessive pattern of inheritance, leading to progressive accumulation of Glycosaminoglycans (GAGs) within lysosomes, resulting in cellular damage and multiorgan dysfunction [1]. Individuals with mucopolysaccharidosis type I (MPS-I Hurler syndrome) cannot degrade GAGs such as dermatan and heparan sulphate, important components of extracellular matrix and cartilaginous tissues including heart valves and joints. Estimated global prevalence of Hurler syndrome is 1 in 100,000 live births usually in early childhood [2,3]. It is characterised by progressive multisystem involvement causing skeletal deformities, dental irregularities, coarse facial features, organ enlargement, and cardiovascular complications [4,5].

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2026-05-25 | RNA activation as a precision dosing modality: MTL-CEBPA for controlled enzyme elevation in MPS I-H.

Gene therapy and hematopoietic stem cell transplantation (HSCT) have transformed outcomes for severe mucopolysaccharidosis type I (MPS I-H), yet a critical unmet need remains. Children with MPS I-H frequently experience progressive skeletal, cardiac, and other complications despite timely HSCT, largely because enzyme activity cannot be safely and precisely titrated over time. Irreversible genetic modification via integrating vectors offers supra-physiological enzyme levels but carries long-term safety and re-dosing liabilities in patients treated early in life. We investigated RNA activation (RNAa) as a precision dosing strategy to enhance endogenous IDUA expression without permanent genome alteration. Using MTL-CEBPA, a small activating RNA that upregulates CEBPA transcription factor, we characterized CEBPA-IDUA relationships in vitro, in vivo, and in legacy clinical samples from cancer patients. CCAAT enhancer binding protein alpha activation consistently increased IDUA mRNA across A549, IMR90, and mesenchymal stem cells. In wild-type mice, two intravenous MTL-CEBPA doses produced a ∼2-fold, durable increase in bone marrow IDUA mRNA and plasma enzyme activity, sustained for up to 4 weeks. In humanized bone marrow-transplanted MPS I-H mice, repeated dosing with MTL-CEBPA led to an approximately 2-fold increase in circulating IDUA activity compared with controls over the 3-weeks treatment period. The largest apparent separation from controls was observed in the homozygous cohort, although these genotype-specific differences should be interpreted cautiously given the limited subgroup sizes. In cancer patient-derived monocytes, increased CEBPA protein levels correlated with higher IDUA levels (R2 = 0.571). Consistent with this, approximately half of evaluable patients exhibited increased plasma IDUA activity following treatment. These translational data demonstrate that MTL-CEBPA delivers controlled, reversible enhancement of IDUA in the context of HSCT, providing robust pharmacodynamic proof-of-concept rather than definitive evidence of durable efficacy. By enabling titratable enzyme elevation without integrating vectors, RNAa therapeutics address a key unmet need in Hurler syndrome: safe fine-tuning of residual enzyme activity over a patient's lifetime. With scalable, cost-effective oligonucleotide manufacturing, MTL-CEBPA and related RNAa therapeutics represent a clinically relevant adjuvant strategy for HSCT-treated MPS I-H, with potential for other enzyme deficiency disorders.

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