Skeletal response to lentiviral mediated gene therapy in a mouse model of MPS VII

Macsai, Carmen E.; Derrick-Roberts, Ainslie L.K.; Ding, Xiaodan; Zarrinkalam, Krystyna H.; McIntyre, Chantelle; Anderson, Paul; Anson, Donald S.; Byers, Sharon

doi:10.1016/j.ymgme.2012.03.022

Cited by 32 publications

(29 citation statements)

References 70 publications

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“…Neonatal and adult gene therapy in MPS VII mice by the use of lentiviral vectors showed improvement in parameters of bone mass and architecture as well as biochemical and enzymatic correction [134]. However, growth plate chondrocytes were not responsive to treatment, as evidenced by the lack of improvement in vertebral and femoral bone length and growth plate height.…”

Section: Mps Vii-gene Therapy Reports For Mps VII Have Used Plasmidmentioning

confidence: 99%

“…Nevertheless, there was limited effect in cervical vertebrae, cervical vertebral fusion, and intervertebral disc degeneration [131].These results showed that an early treatment with a long-term supraphysiological enzyme activity levels was not able to completely resolve all skeletal abnormalities. [132] sleeping beauty transposon [117], gamma-retroviral [120,121,132,133], lentiviral [134], and AAV [135,136] vectors. Favorable results for bone lesions were reported in MPS VII dogs by neonatal gene therapy using a gamma-retroviral vector [133].…”

Section: Mps Vi-mentioning

confidence: 99%

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Therapies for the bone in mucopolysaccharidoses

Tomatsu

Barrera

Alméciga-Díaz

et al. 2015

Molecular Genetics and Metabolism

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Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required.Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life.This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs.

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Section: Mps Vii-gene Therapy Reports For Mps VII Have Used Plasmidmentioning

confidence: 99%

Section: Mps Vi-mentioning

confidence: 99%

Therapies for the bone in mucopolysaccharidoses

Tomatsu

Barrera

Alméciga-Díaz

et al. 2015

Molecular Genetics and Metabolism

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show abstract

“…In another example, RV-mediated liver-directed expression of b-glucuronidase resulted in significantly increased survival and long-term expression (11 years) in both the murine and canine models of MPS VII. However, unlike in the murine model, treated MPS VII dogs still developed lumbar spinal disease, which is thought to be due to the inability of the secreted enzyme to reach and cross-correct the spine tissues (Macsai et al, 2012;Smith et al, 2012). Together these studies suggest that strategies may not translate in a linear fashion as we move from preclinical studies in small to large animal models of disease to clinical trials.…”

Section: Retroviral Vectorsmentioning

confidence: 99%

Gene Therapy Approaches for Lysosomal Storage Disease: Next-Generation Treatment

et al. 2012

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“…After 3 h 50% of the cells were transduced with 0.007, 0.035 or 0.07 μg/μL p24 protein of pHIV-EF1αmmGUS. When cells reached 80% confluency one half of the cells were fixed in chloral-formal acetone for 30 min at 4°C and stained for β-D-glucuronidase activity, as previously described [43,44]. Transduction efficiency was determined by counting pink (transduced) and clear (non-transduced) cells for each well.…”

Section: Time Course Of β-D-glucuronidase Transductionmentioning

confidence: 99%