Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs

Dell’Agnola, Chiara; Wang, Zejing; Storb, Rainer; Tapscott, Stephen J.; Kuhr, Christian S.; Hauschka, Stephen D.; Lee, Richard S.; Sale, George E.; Zellmer, Eustacia; Gisburne, Serina; Bogan, Janet R.; Kornegay, Joe N.; Cooper, Barry; Gooley, Theodore A.; Little, Marie Térèse

doi:10.1182/blood-2004-06-2247

Cited by 72 publications

(56 citation statements)

References 38 publications

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“…Conclusions and future perspectives Gene or cell therapy approaches for GRMD have until now produced negative 20 or modestly positive results [21][22][23] . We show here that it is possible to transplant mesoangioblasts into dystrophic dogs and obtain an extensive reconstitution of fibres expressing dystrophin, an improvement in the contraction force and, in many cases, a preservation of walking ability.…”

Section: Immune Reaction Against Dystrophin and Donor Cellsmentioning

confidence: 99%

Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Sampaolesi

Blot

D’Antona

et al. 2006

Nature

675

569

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Duchenne muscular dystrophy remains an untreatable genetic disease that severely limits motility and life expectancy in affected children. The only animal model specifically reproducing the alterations in the dystrophin gene and the full spectrum of human pathology is the golden retriever dog model. Affected animals present a single mutation in intron 6, resulting in complete absence of the dystrophin protein, and early and severe muscle degeneration with nearly complete loss of motility and walking ability. Death usually occurs at about 1 year of age as a result of failure of respiratory muscles. Here we report that intra-arterial delivery of wild-type canine mesoangioblasts (vessel-associated stem cells) results in an extensive recovery of dystrophin expression, normal muscle morphology and function (confirmed by measurement of contraction force on single fibres). The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients.

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Section: Immune Reaction Against Dystrophin and Donor Cellsmentioning

confidence: 99%

Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Sampaolesi

Blot

D’Antona

et al. 2006

Nature

675

569

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show abstract

“…Many treatments have been attempted in the last 20 years, but they all have failed (Hoffman and Dressman, 2001;Dell'Agnola et al, 2004;Liu et al, 2004). New therapies are still under investigation, some of which are based on animal models (Dell'Agnola et al, 2004;McClorey et al, 2006;Kerkis et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Identification of three distinguishable phenotypes in golden retriever muscular dystrophy

Ambrósio

Fadel²,

Gaiad³

et al. 2009

Genet. Mol. Res.

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ABSTRACT. Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter-and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.

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“…In observation periods ranging from 28 to 417 days after transplantation of normal hematopoietic cells in 7 dogs with dystrophin-deficient muscular dystrophy, there was no evidence nor for participation in myofiber regeneration neither for formation of myogenic mononuclear cells [89]. There were also two clinical cases in which the reconstitution of the hematopoietic compartment with cells of a normal donor confirmed the inefficiency of this approach.…”

Section: Heterodox Myogenic Cellsmentioning

confidence: 63%

“…The inefficiency of hematopoietic cell transplantation to participate in myofiber regeneration and to induce donorderived dystrophin expression was confirmed in dogs [89]. In observation periods ranging from 28 to 417 days after transplantation of normal hematopoietic cells in 7 dogs with dystrophin-deficient muscular dystrophy, there was no evidence nor for participation in myofiber regeneration neither for formation of myogenic mononuclear cells [89].…”

Section: Heterodox Myogenic Cellsmentioning

confidence: 82%

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

Skuk

2013

ISRN Transplantation

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Myopathies produce deficits in skeletal muscle function and, in some cases, progressive and irreversible loss of skeletal muscles. The transplantation of myogenic cells, that is, cells able to differentiate into myofibers, is an experimental strategy for the potential treatment of some of these diseases. The objectives pursued by the transplantation of these cells are essentially three: (a) the fusion with the patient's myofibers to obtain the expression of therapeutic proteins into them, (b) the neoformation of new functional myofibers in skeletal muscles that were too degenerated by the progressive degeneration, and (c) the formation of a new pool of healthy donor-derived satellite cells. Although the repertoire of myogenic cells appears to have expanded in recent years, myoblasts are the only cells that have been demonstrated to engraft in humans. The present work aims to make a comprehensive review of the subject, from its beginnings to recent advances, including the preclinical experience in different animal models and recent clinical findings.

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Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs

Cited by 72 publications

References 38 publications

Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs

Identification of three distinguishable phenotypes in golden retriever muscular dystrophy

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

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