Helper-dependent canine adenovirus vector-mediated transgene expression in a neurodegenerative lysosomal storage disorder

Lau, Adeline A.; Rozaklis, Tina; Ibanes, Sandy; Luck, Amanda; Beard, Helen; Hassiotis, Sofia; Mazouni, Khalil; Hopwood, John J.; Kremer, Eric J.; Hemsley, Kim M.

doi:10.1016/j.gene.2011.09.004

Cited by 23 publications

(16 citation statements)

References 25 publications

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“…numerous areas of the MPS IIIA mouse brain [48,49]. In another line of therapy, a CAV-2 vector expressing neuroglobin, in combination with a c-Jun N-terminal kinase inhibitor, protects against oxidative stress and neuronal apoptosis induced by stroke in hypertensive rats [50].…”

Section: Cav-2 Vectors To Understand and Treat Neurodegenerative Disementioning

confidence: 99%

CAV-2—why a canine virus is a neurobiologist's best friend

Junyent

Kremer

2015

Current Opinion in Pharmacology

101

100

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Section: Cav-2 Vectors To Understand and Treat Neurodegenerative Disementioning

confidence: 99%

CAV-2—why a canine virus is a neurobiologist's best friend

Junyent

Kremer

2015

Current Opinion in Pharmacology

101

100

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“…HD CAdV-2 was determined to have the most promising vector profile: equal transduction efficacy, no negative effect to neuronal development, and milder induced immune response (Piersanti et al, 2013). HD CAdV-2 was also used as a vector in order to evaluate a gene therapy approach to correct the neurodegenerative lysosomal storage disorder mucopolysaccharidosis type IIIa (Lau et al, 2012). It was shown to effectively transduce neurons and provide long-term transgene expression; however, its use in vivo was limited to discrete areas of the brain, indicating a need to find a way to increase transgene expression throughout the whole brain.…”

Section: Canine Adv Vectorsmentioning

confidence: 99%

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

et al. 2014

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Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles.

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“…Therefore, studies on gene therapy for MPS III have mainly focused on the correction of the neurodegeneration. As shown in Table 1, AAV [66,70-75], lentivirus [70,76-78] and canine adenovirus (AdV) vectors [79,80] have been evaluated for MPS IIIA and IIIB gene therapies, which have been delivered intravenously or by direct brain injection (i.e., intracranial, intraventricular, intracisternal or intracranial). A common approach for the treatment of MPS III was intravenous pretreatment with mannitol, which in most cases allowed an increase of the number of transduced cells in both brain and peripheral organs, as well as improvement of the therapeutic effect of the therapy [71,72,75,78].…”

Section: Advanced Therapies For Morquio a Syndromementioning

confidence: 99%

“…A common approach for the treatment of MPS III was intravenous pretreatment with mannitol, which in most cases allowed an increase of the number of transduced cells in both brain and peripheral organs, as well as improvement of the therapeutic effect of the therapy [71,72,75,78]. Except for the studies carried out with canine AdV vector [79,80], gene therapy for MPS IIIA and IIIB showed long-term vector maintenance and expression, improvement in behavioral performance, reduction of GAG in urine and/or tissues, increase in life span and normalization of secondary enzymatic activities (e.g., β-glucuronidase or β-hexosaminidase). Nevertheless, enzymatic activity in serum and tissues ranged between normal and subnormal levels, showing that supraphysiological enzymatic activities are not required to achieve a therapeutic effect in MPS III.…”

Section: Advanced Therapies For Morquio a Syndromementioning

confidence: 99%

Therapies of mucopolysaccharidosis IVA (Morquio A syndrome)

Tomatsu

Alméciga-Díaz

Barbosa

et al. 2013

Expert Opinion on Orphan Drugs

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Introduction Morquio A syndrome (mucopolysaccharidosis type IVA, MPS IVA) is one of the lysosomal storage diseases and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme leads to accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced by chondrocytes, and therefore, the undegraded substrates accumulate mainly in cells and extracelluar matrix (ECM) of cartilage. This has a direct impact on cartilage and bone development, leading to systemic skeletal dysplasia. In patients with Morquio A, cartilage cells are vacuolated, and this results in abnormal chondrogenesis and/or endochondral ossification. Areas covered This article describes the advanced therapies of Morquio A, focused on enzyme replacement therapy (ERT) and gene therapy to deliver the drug to avascular bone lesions. ERT and gene therapies for other types of MPS are also discussed, which provide therapeutic efficacy to bone lesions. Expert opinion ERT, gene therapy and hematopietic stem therapy are clinically and/or experimentally conducted. However, there is no effective curative therapy for bone lesion to date. One of the limitations for Morquio A therapy is that targeting avascular cartilage tissues remains an unmet challenge. ERT or gene therapy with bone-targeting system will improve the bone pathology and skeletal manifestations more efficiently.

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Helper-dependent canine adenovirus vector-mediated transgene expression in a neurodegenerative lysosomal storage disorder

Cited by 23 publications

References 25 publications

CAV-2—why a canine virus is a neurobiologist's best friend

CAV-2—why a canine virus is a neurobiologist's best friend

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

Therapies of mucopolysaccharidosis IVA (Morquio A syndrome)

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