Addressing the Value of Gene Therapy and Enhancing Patient Access to Transformative Treatments

Salzman, Rachel; Cook, Francesca; Hunt, Timothy D.; Malech, Harry L.; Reilly, Philip R.; Foss-Campbell, Betsy; Barrett, David M.

doi:10.1016/j.ymthe.2018.10.017

Cited by 74 publications

(82 citation statements)

References 14 publications

(22 reference statements)

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“…Current definitions of gene therapy have changed due to recent technical advances in genetic engineering of cells. Presently, potential treatments include vector-delivered gene therapy, gene-modified cell therapy and gene editing (Salzman et al, 2018 ). Salzman et al summarized the clinical aim of these treatment concepts succinctly: “Rather than treating disease symptoms, gene therapy can address the root causes of genetic diseases by modifying expression of a patient's genes or by repairing or replacing abnormal genes.” (Salzman et al, 2018 ).…”

Section: Methods To Enhance the Function Of Harvested Cells (mentioning

confidence: 99%

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Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches

Goodman

Lin

2020

Front. Bioeng. Biotechnol.

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Healing of fractures and bone defects normally follows an orderly series of events including formation of a hematoma and an initial stage of inflammation, development of soft callus, formation of hard callus, and finally the stage of bone remodeling. In cases of severe musculoskeletal injury due to trauma, infection, irradiation and other adverse stimuli, deficient healing may lead to delayed or non-union; this results in a residual bone defect with instability, pain and loss of function. Modern methods of mechanical stabilization and autologous bone grafting are often successful in achieving fracture union and healing of bone defects; however, in some cases, this treatment is unsuccessful because of inadequate biological factors. Specifically, the systemic and local microenvironment may not be conducive to bone healing because of a loss of the progenitor cell population for bone and vascular lineage cells. Autologous bone grafting can provide the necessary scaffold, progenitor and differentiated lineage cells, and biological cues for bone reconstruction, however, autologous bone graft may be limited in quantity or quality. These unfavorable circumstances are magnified in systemic conditions with chronic inflammation, including obesity, diabetes, chronic renal disease, aging and others. Recently, strategies have been devised to both mitigate the necessity for, and complications from, open procedures for harvesting of autologous bone by using minimally invasive aspiration techniques and concentration of iliac crest bone cells, followed by local injection into the defect site. More elaborate strategies (not yet approved by the U.S. Food and Drug Administration-FDA) include isolation and expansion of subpopulations of the harvested cells, preconditioning of these cells or inserting specific genes to modulate or facilitate bone healing. We review the literature pertinent to the subject of modifying autologous harvested cells including MSCs to facilitate bone healing. Although many of these techniques and technologies are still in the preclinical stage and not yet approved for use in humans by the FDA, novel approaches to accelerate bone healing by modifying cells has great potential to mitigate the physical, economic and social burden of non-healing fractures and bone defects.

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Section: Methods To Enhance the Function Of Harvested Cells (mentioning

confidence: 99%

“…Salzman et al summarized the clinical aim of these treatment concepts succinctly: "Rather than treating disease symptoms, gene therapy can address the root causes of genetic diseases by modifying expression of a patient's genes or by repairing or replacing abnormal genes." (Salzman et al, 2018).…”

Section: Genetic Manipulation Of Cellsmentioning

confidence: 99%

Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches

Goodman

Lin

2020

Front. Bioeng. Biotechnol.

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“…The pricing for a curative medicine that is administered only once to a given patient is still subject to much debate. Fair pricing that societies can afford (for instance via health insurance reimbursement) must be balanced against the profits needed by biotech and pharma companies to survive (69). This may require new financial models that feature responsible entrepreneurship and access to treatments for patients.…”

Section: Future Perspectivesmentioning

confidence: 99%

Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives

2019

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Gene therapy using patient's own stem cells is rapidly becoming an alternative to allogeneic stem cell transplantation, especially when suitably compatible donors cannot be found. The advent of efficient virus-based methods for delivering therapeutic genes has enabled the development of genetic medicines for inherited disorders of the immune system, hemoglobinopathies, and a number of devastating metabolic diseases. Here, we briefly review the state of the art in the field, including gene editing approaches. A growing number of pediatric diseases can be successfully cured by hematopoietic stem-cell-based gene therapy.

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“…As has happened with the approval of Strimvelis for the treatment of ADA‐SCID patients, several new approvals of medicinal products based on the genetic correction of HSCs will appear in upcoming years. Discussions about the efficacy and safety of gene therapy are rapidly moving toward additional questions related to the cost of these new therapies and the procedures that should be used to facilitate the spread of these new therapies to patients . Shall patients travel to specialized gene therapy institutions, or shall these new medicinal products be delivered under appropriate conditions to facilitate its application in local institutions?…”

Section: Perspectives Of Hematopoietic Gene Therapymentioning

confidence: 99%

Advances in the gene therapy of monogenic blood cell diseases

et al. 2019

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Hematopoietic gene therapy has markedly progressed during the last 15 years both in terms of safety and efficacy. While a number of serious adverse events (SAE) were initially generated as a consequence of genotoxic insertions of gamma-retroviral vectors in the cell genome, no SAEs and excellent outcomes have been reported in patients infused with autologous hematopoietic stem cells (HSCs) transduced with self-inactivated lentiviral and gammaretroviral vectors. Advances in the field of HSC gene therapy have extended the number of monogenic diseases that can be treated with these approaches. Nowadays, evidence of clinical efficacy has been shown not only in primary immunodeficiencies, but also in other hematopoietic diseases, including beta-thalassemia and sickle cell anemia. In addition to the rapid progression of non-targeted gene therapies in the clinic, new approaches based on gene editing have been developed thanks to the discovery of designed nucleases and improved non-integrative vectors, which have markedly increased the efficacy and specificity of gene targeting to levels compatible with its clinical application. Based on advances achieved in the field of gene therapy, it can be envisaged that these therapies will soon be part of the therapeutic approaches used to treat life-threatening diseases of the hematopoietic system.

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Addressing the Value of Gene Therapy and Enhancing Patient Access to Transformative Treatments

Cited by 74 publications

References 14 publications

Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches

Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches

Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives

Advances in the gene therapy of monogenic blood cell diseases

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