Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

Bartoli, Marc; Poupiot, Jérôme; Goyenvalle, Aurélie; Pérez, Norma; Garcı́a, Luis; Danos, Olivier; Richard, Isabelle

doi:10.1038/sj.gt.3302594

Cited by 29 publications

(20 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The level of expression obtained with this vector is equivalent to the expression of a reporter transgene, such as mSeAP and much lower than a therapeutic one injected at the same age. 38 As an explanation, it can be suggested that any propeptide that may be expressed in fibers did not circumvent the membrane-related degenerative process. This hypothesis is consistent with the absence of reversal of stretch sensitivity observed in the mdx mice after pharmacological blockade of myostatin, 26,28 suggesting that membrane destabilization persists even if the muscle is stronger.…”

Section: Discussionmentioning

confidence: 99%

AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency

et al. 2007

Self Cite

View full text Add to dashboard Cite

Myostatin is a negative regulator of muscle mass whose inhibition has been proposed as a therapeutic strategy for muscle-wasting conditions. Indeed, blocking myostatin action through different strategies has proved beneficial for the pathophysiology of the dystrophin-deficient mdx mouse. In this report, we tested the inhibition of myostatin by AAV-mediated expression of a mutated propeptide in animal models of two limb-girdle muscular dystrophies:LGMD2A caused by mutations in the calpain 3 (CAPN3) gene and LGMD2D caused by mutations in the a-sarcoglycan gene (SGCA). In the highly regenerative Sgca-null mice, survival of the a-sarcoglycan-deficient muscle fibers did not improve after transfer of the myostatin propeptide. In calpain 3-deficient mice, a boost in muscle mass and an increase in absolute force were obtained, suggesting that myostatin inhibition could constitute a therapeutic strategy in this predominantly atrophic disorder.

show abstract

Section: Discussionmentioning

confidence: 99%

AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following this, simple blood-based assay of Se AP can predict gene expression in specific muscles. The assay overcomes limitations of CK level identification that is nonspecific and minimally affected in cases of local delivery of the gene (84). Another approach measures dysferlin and calpain 3 expression levels using circulating monocytes that reflect expression level sin muscles given that the target therapy is delivered systemically (61).…”

Section: Disease Markersmentioning

confidence: 99%

Limb-girdle muscular dystrophies: Where next after six decades from the first proposal (Review)

Mahmood

Jiang

2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of disorders, which has led to certain investigators disputing its rationality. The mutual feature of LGMD is limb-girdle affection. Magnetic resonance imaging (MRI), perioral skin biopsies, blood-based assays, reverse-protein arrays, proteomic analyses, gene chips and next generation sequencing are the leading diagnostic techniques for LGMD and gene, cell and pharmaceutical treatments are the mainstay therapies for these genetic disorders. Recently, more highlights have been shed on disease biomarkers to follow up disease progression and to monitor therapeutic responsiveness in future trials. In this study, we review LGMD from a variety of aspects, paying specific attention to newly evolving research, with the purpose of bringing this information into the clinical setting to aid the development of novel therapeutic strategies for this hereditary disease. In conclusion, substantial progress in our ability to diagnose and treat LGMD has been made in recent decades, however enhancing our understanding of the detailed pathophysiology of LGMD may enhance our ability to improve disease outcome in subsequent years.

show abstract

“…Several soluble marker peptides have proven their worth in this regard, such as secreted alkaline phosphatase, alphafetoprotein, β hCG and sCEA [14,37–39]. In choosing a suitable marker polypeptide, the key parameters to consider are its antigenic potential, biological activity, ease of detection in body fluids, baseline circulating levels and kinetics of elimination from the body.…”

Section: Discussionmentioning

confidence: 99%

Concordant activity of transgene expression cassettes inserted into E1, E3 and E4 cloning sites in the adenovirus genome

Pham

Nakamura

Rosales

et al. 2009

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background Expression cassettes can be inserted at several positions into recombinant adenoviral genomes but the implications of this choice for transgene expression level have not been determined. Knowledge of the relative expression levels of transgenes inserted at different sites in the adenoviral genome is of particular significance for transgene expression monitoring approaches that rely on the concordant expression of a marker transgene inserted elsewhere in the viral genome. Methods Three expression cassettes, each comprising a cytomegalovirus promoter driving one of three marker peptides [serum carcinoembryonic antigen (sCEA), beta subunit of human chorionic gonadotropin (βhCG) or human sodium iodide symporter (hNIS)], were inserted into E1, E3 or E4 cloning sites in a recombinant adenoviral vector backbone. High titer stocks of bicistronic adenoviral vectors coding for combinations of marker peptides were prepared. A panel of human cells of various lineages was infected with the vectors and expression ratios of the transgene-encoded proteins were analysed. Serum levels of the soluble proteins and hepatic uptake of radioactive iodine were also compared in vivo in nude rats after intravenous vector infusion. Results High concordance of expression between the inserted transgenes was observed in all of the bicistronic vectors irrespective of whether the expression cassettes were placed in the E1, E3 or E4 regions. Concordance was maintained across multiple cell lineages. In vivo, in athymic rats, blood and urine levels of βhCG were highly concordant with serum levels of sCEA at all timepoints after intravenous infusion of the bicistronic vectors encoding both of these soluble markers. Hepatic radioiodine uptake was concordant with serum CEA concentration in mice infused with a bicistronic vector expressing CEA and NIS. Conclusions The expression level of a given transgene in an adenoviral vector genome can be accurately and quantitatively inferred from the expression of a marker protein encoded by a second transgene inserted elsewhere in the vector genome.

show abstract

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

Cited by 29 publications

References 49 publications

AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency

AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency

Limb-girdle muscular dystrophies: Where next after six decades from the first proposal (Review)

Concordant activity of transgene expression cassettes inserted into E1, E3 and E4 cloning sites in the adenovirus genome

Contact Info

Product

Resources

About