Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders

Xing, Minzhi; Parker, E I; Moreno-De-Luca, Andrés; Harmouche, Elie; Terk, Michael R.

doi:10.1259/bjr.20130467

Cited by 19 publications

(1 citation statement)

References 44 publications

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“…Accumulation of these undegraded lysosomal substrates results in widespread tissue pathology, often characterized by skeletal deformities, cardiac and pulmonary disease, upper airway obstruction, and in some cases, progressive neurological disease. 1 The central nervous system manifestations of MPS I vary, with profound developmental decline occurring in early childhood in severely affected patients, while those with a more mild phenotype often maintain normal intelligence. [2][3][4][5][6][7] However, even the patients with attenuated disease sometimes face serious neurological complications such as communicating hydrocephalus, as well as spinal cord compression secondary to GAG storage in the meninges.…”

Section: Introductionmentioning

confidence: 99%

Intrathecal Gene Therapy Corrects CNS Pathology in a Feline Model of Mucopolysaccharidosis I

et al. 2014

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Enzyme replacement therapy has revolutionized the treatment of the somatic manifestations of lysosomal storage diseases (LSD), although it has been ineffective in treating central nervous system (CNS) manifestations of these disorders. The development of neurotrophic vectors based on novel serotypes of adeno-associated viruses (AAV) such as AAV9 provides a potential platform for stable and efficient delivery of enzymes to the CNS. We evaluated the safety and efficacy of intrathecal delivery of AAV9 expressing α-l-iduronidase (IDUA) in a previously described feline model of mucopolysaccharidosis I (MPS I). A neurological phenotype has not been defined in these animals, so our analysis focused on the biochemical and histological CNS abnormalities characteristic of MPS I. Five MPS I cats were dosed with AAV9 vector at 4-7 months of age and followed for 6 months. Treated animals demonstrated virtually complete correction of biochemical and histological manifestations of the disease throughout the CNS. There was a range of antibody responses against IDUA in this cohort which reduced detectable enzyme without substantially reducing efficacy; there was no evidence of toxicity. This first demonstration of the efficacy of intrathecal gene therapy in a large animal model of a LSD should pave the way for translation into the clinic.

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Section: Introductionmentioning

confidence: 99%

Intrathecal Gene Therapy Corrects CNS Pathology in a Feline Model of Mucopolysaccharidosis I

et al. 2014

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Orofacial abnormalities in mucopolysaccharidosis and mucolipidosis typeIIandIII: A systematic review

et al. 2022

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Mucopolysaccharidoses (MPSs) and mucolipidosis II and III (ML II and III) often manifest with orofacial (progressive) abnormalities, which may have a major impact on quality of life. However, because these patients have multiple somatic health issues, orofacial problems are easily overlooked in clinical practice and available literature on this topic solely consists of case reports, small case series, and small cohort studies. The aim of this systematic review was to gain more insight in the nature and extent of orofacial abnormalities in MPS, ML II, and III. A systematic review of all previously published articles addressing orofacial abnormalities in MPS, ML II, and III was performed. Both clinical studies and case reports were included. Outcome was the described orofacial abnormalities, subdivided into abnormalities of the face, maxilla, mandible, soft tissues, teeth, and occlusion. The search resulted in 57 articles, describing orofacial features in 340 patients. Orofacial abnormalities were present in all subtypes of MPS, ML II, and III, and consisted of thickened lips, a hypoplastic midface, a high‐arched palate, hypoplastic condyles, coronoid hyperplasia, macroglossia, gingival hyperplasia, thick dental follicles, dentigerous cysts, misshapen teeth, enamel defects, and open bite. Orofacial abnormalities are present in all subtypes of MPS, ML II, and III. As orofacial abnormalities may cause complaints, evaluation of orofacial health should be part of routine clinical care.

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Spleen and Peritoneal Cavity

Duffy

Castro-Aragon

Tivnan

et al. 2021

Pediatric Ultrasound

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Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders

Cited by 19 publications

References 44 publications

Intrathecal Gene Therapy Corrects CNS Pathology in a Feline Model of Mucopolysaccharidosis I

Intrathecal Gene Therapy Corrects CNS Pathology in a Feline Model of Mucopolysaccharidosis I

Orofacial abnormalities in mucopolysaccharidosis and mucolipidosis typeIIandIII: A systematic review

Spleen and Peritoneal Cavity

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