Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication

Деев, Р. В.; Plaksa, Igor; Бозо, И Я; Mzhavanadze, N.D.; Suchkov, I.А.; Chervyakov, Yuriy V.; Староверов, И Н; Каlinin, R.E.; Исаев, А. А.

doi:10.1177/1753944718786926

Cited by 35 publications

(21 citation statements)

References 11 publications

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“…Intramuscular injection of a single dose of this drug, costing less than $50, delivers a plasmid DNA-carrying VEGF gene cloned under a CMV promoter and stimulates angiogenesis and blood supply to decrease the risk of amputation and death in patients suffering from PAD. A recent post-marketing surveillance study revealed a significant increase in pain-free walking distance by PAD patients and confirmed the therapeutic efficacy of this drug (56, 57). Recently, Spinraza® has become the first approved treatment for the rare and often fatal disease spinal muscular atrophy (SMA).…”

Section: Gene Therapy Drugs In the Marketmentioning

confidence: 63%

“…In situ delivery, or “in position” delivery, involves administration of the desired genetic material directly into the target cells or tissue. For example, Neovasculgen®, a plasmid vector carrying vascular endothelial growth factor (VEGF) gene, is directly injected into the target ischemic tissue to stimulate blood vessel growth (55–57). This method is being explored to cure cystic fibrosis, muscular dystrophy, and cancer but still requires more technological advancement in delivery methods for a successful clinical outcome (58–60).…”

Section: Somatic Cell Gene Therapymentioning

confidence: 99%

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Gene Therapy Leaves a Vicious Cycle

et al. 2019

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The human genetic code encrypted in thousands of genes holds the secret for synthesis of proteins that drive all biological processes necessary for normal life and death. Though the genetic ciphering remains unchanged through generations, some genes get disrupted, deleted and or mutated, manifesting diseases, and or disorders. Current treatment options—chemotherapy, protein therapy, radiotherapy, and surgery available for no more than 500 diseases—neither cure nor prevent genetic errors but often cause many side effects. However, gene therapy, colloquially called “living drug,” provides a one-time treatment option by rewriting or fixing errors in the natural genetic ciphering. Since gene therapy is predominantly a viral vector-based medicine, it has met with a fair bit of skepticism from both the science fraternity and patients. Now, thanks to advancements in gene editing and recombinant viral vector development, the interest of clinicians and pharmaceutical industries has been rekindled. With the advent of more than 12 different gene therapy drugs for curing cancer, blindness, immune, and neuronal disorders, this emerging experimental medicine has yet again come in the limelight. The present review article delves into the popular viral vectors used in gene therapy, advances, challenges, and perspectives.

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Section: Gene Therapy Drugs In the Marketmentioning

confidence: 63%

Section: Somatic Cell Gene Therapymentioning

confidence: 99%

Gene Therapy Leaves a Vicious Cycle

et al. 2019

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“…Some of the common side effects reported in patients receiving Zynteglo TM during the clinical trials were a low count of thrombocytes, numbness in hands and feet, pain in the bone, nausea, headache, and low blood calcium levels ( Deev et al, 2018 ).…”

Section: Safety and Efficacy Of Advanced Therapy Medicinal Products (mentioning

confidence: 99%

Two Decades of Global Progress in Authorized Advanced Therapy Medicinal Products: An Emerging Revolution in Therapeutic Strategies

Ramezankhani

Torabi

Minaei

et al. 2020

Front. Cell Dev. Biol.

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The introduction of advanced therapy medicinal products (ATMPs) to the global pharma market has been revolutionizing the pharmaceutical industry and has opened new routes for treating various types of cancers and incurable diseases. In the past two decades, a noticeable part of clinical practices has been devoting progressively to these products. The first step to develop such an ATMP product is to be familiar with other approved products to obtain a general view about this industry trend. The present paper depicts an overall perspective of approved ATMPs in different countries, while reflecting the degree of their success in a clinical point of view and highlighting their main safety issues and also related market size as a whole. In this regard, published articles regarding safety, efficacy, and market size of approved ATMPs were reviewed using the search engines PubMed, Scopus, and Google Scholar. For some products which the related papers were not available, data on the relevant company website were referenced. In this descriptive study, we have introduced and classified approved cell, gene, and tissue engineering-based products by different regulatory agencies, along with their characteristics, manufacturer, indication, approval date, related regulatory agency, dosage, product description, price and published data about their safety and efficacy. In addition, to gain insights about the commercial situation of each product, we have gathered accessible sale reports and market size information that pertain to some of these products.

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“…Considering the crucial role of VEGF-A in reparative osteogenesis, the osteoconductive potential of OCP, and our experience in gene-therapeutic drug development and clinical translation (Deev et al, 2018 ), we aimed to investigate and clinically translate a gene-activated bone substitute based on an OCP scaffold and VEGFA165 -carrying plasmid DNA (pDNA- VEGF ).…”

Section: Introductionmentioning

confidence: 99%

Bringing a Gene-Activated Bone Substitute Into Clinical Practice: From Bench to Bedside

Бозо

Drobyshev

Redko

et al. 2021

Front. Bioeng. Biotechnol.

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Bone grafting and reconstruction are still challenging in clinical practice because of the limitations of bone autografts and the drawbacks of currently approved bone substitutes. We thus developed a gene-activated bone substitute based on octacalcium phosphate and naked plasmid DNA carrying the vascular endothelial growth factor gene. This advanced combined therapy medicinal product had no cytotoxic effects in vitro, slightly decreased bone marrow mesenchymal stromal cell (MSC) doubling time, and was characterized by a prolonged level of gene construct delivery in vivo in a luciferase bioimaging assay. In the model of critically sized cranial bone defects in rabbits, the gene-activated matrix increased bone tissue formation through angiogenesis induction. After preclinical studies, we conducted an open-label non-randomized clinical trial (NCT03076138). The primary study outcome was the proportion of patients with newly formed bone tissue within the surgical area as measured by computed tomography within 6 months after surgery. The main secondary outcomes included frequencies of adverse events (AEs) and serious adverse events (SAEs) as well as the surgical failure rate. After completing the clinical trial, the patients had dental implants placed in the bone grafting area, and trephine biopsy samples were collected. In total, 20 patients with alveolar ridge atrophy (n = 16) and jaw bone defects (n = 4) were enrolled in the study. There were no AEs or SAEs during the clinical trial or the follow-up period (30 months). In all patients, newly formed tissues with a bone density of 908.13 ± 114.40 HU were detected within the zone of bone grafting. There were no significant differences between the subgroups of patients with atrophy and bone defects: 915.28 ± 125.85 and 879.56 ± 48.36 HU, respectively (p = 0.60). Histological analysis showed that the bone grafting area comprised newly formed bone tissue with some fragments of the gene-activated bone substitute partially resorbed and integrated with bone, without fibrous tissue in between. The preclinical data and clinical trial results proved the feasibility, safety, and efficacy of the investigated material for jaw bone grafting, allowing us to bring the world's first gene-activated bone substitute from bench to bedside.

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Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication

Abstract: The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.

Cited by 35 publications

References 11 publications

Gene Therapy Leaves a Vicious Cycle

Gene Therapy Leaves a Vicious Cycle

Two Decades of Global Progress in Authorized Advanced Therapy Medicinal Products: An Emerging Revolution in Therapeutic Strategies

Bringing a Gene-Activated Bone Substitute Into Clinical Practice: From Bench to Bedside

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