ArticlePloS one2011
Anti-TNF-alpha therapy enhances the effects of enzyme replacement therapy in rats with mucopolysaccharidosis type VI.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Metabolic masqueraders of paediatric and adult rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Neuroinflammation as a Novel Therapeutic Frontier for Sanfilippo Syndrome.Children (Basel, Switzerland) · 2025Review
- Rat models of musculoskeletal lysosomal storage disorders and their role in pre-clinical evaluation of gene therapy approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Single-cell RNA sequencing reveals important role of monocytes and macrophages during mucopolysaccharidosis treatment.Scientific reports · 2025Article
- Endocannabinoid receptor 2 is a potential biomarker and therapeutic target for the lysosomal storage disorders.Journal of inherited metabolic disease · 2025Article
- Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy.International journal of molecular sciences · 2024Review
- An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis.Pharmaceutics · 2023Article
- The Interplay of Glycosaminoglycans and Cysteine Cathepsins in Mucopolysaccharidosis.Biomedicines · 2023Review
- Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets.International journal of molecular sciences · 2022Review
- Mucopolysaccharidosis: What Pediatric Rheumatologists and Orthopedics Need to Know.Diagnostics (Basel, Switzerland) · 2022Review
- MPSI Manifestations and Treatment Outcome: Skeletal Focus.International journal of molecular sciences · 2022Review
- Innate Immunity in Mucopolysaccharide Diseases.International journal of molecular sciences · 2022Review
- Early enzyme replacement therapy prevents dental and craniofacial abnormalities in a mouse model of mucopolysaccharidosis type VI.Frontiers in physiology · 2022Article
- The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy.Frontiers in pharmacology · 2022Review
- Non-cardiac Manifestations in Adult Patients With Mucopolysaccharidosis.Frontiers in cardiovascular medicine · 2022Review
- Mucopolysaccharidosis Type VI, an Updated Overview of the Disease.International journal of molecular sciences · 2021Review
- Bone Biomarkers in Mucopolysaccharidoses.International journal of molecular sciences · 2021Review
- Plasma Proteomic Analysis in Morquio A Disease.International journal of molecular sciences · 2021Article
- Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I.JIMD reports · 2021Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlthough enzyme replacement therapy (ERT) is available for several lysosomal storage disorders, the benefit of this treatment to the skeletal system is very limited. Our previous work has shown the importance of the Toll-like receptor 4/TNF-alpha inflammatory pathway in the skeletal pathology of the mucopolysaccharidoses (MPS), and we therefore undertook a study to examine the additive benefit of combining anti-TNF-alpha therapy with ERT in a rat model of MPS type VI. METHODOLOGY/PRINCIPAL
findingsMPS VI rats were treated for 8 months with Naglazyme® (recombinant human N-acetyl-galactosamine-4-sulfatase), or by a combined protocol using Naglazyme® and the rat-specific anti-TNF-alpha drug, CNTO1081. Both protocols led to markedly reduced serum levels of TNF-alpha and RANKL, although only the combined treatment reduced TNF-alpha in the articular cartilage. Analysis of cultured articular chondrocytes showed that the combination therapy also restored collagen IIA1 expression, and reduced expression of the apoptotic marker, PARP. Motor activity and mobility were improved by ERT, and these were significantly enhanced by combination treatment. Tracheal deformities in the MPS VI animals were only improved by combination therapy, and there was a modest improvement in bone length. Ceramide levels in the trachea also were markedly reduced. MicroCT analysis did not demonstrate any significant positive effects on bone microarchitecture from either treatment, nor was there histological improvement in the bone growth plates. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that combining ERT with anti-TNF-alpha therapy improved the treatment outcome and led to significant clinical benefit. They also further validate the usefulness of TNF-alpha, RANKL and other inflammatory molecules as biomarkers for the MPS disorders. Further evaluation of this combination approach in other MPS animal models and patients is warranted.
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