Recent Advancements in Cardiovascular Gene Therapy and Vascular Biology

Laakkonen, Johanna P.; Ylä‐Herttuala, Seppo

doi:10.1089/hum.2015.095

Cited by 21 publications

(8 citation statements)

References 65 publications

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“…Achieving safe, long-term expression continues to prove a challenge in monogenic disorders (2). Within cardiovascular disease, VEGF gene therapy is being applied to coronary artery disease (13).…”

Section: What Is Gene Therapy? (B)mentioning

confidence: 99%

Placenta-directed gene therapy for fetal growth restriction

Krishnan

David

2017

Seminars in Fetal and Neonatal Medicine

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Fetal growth restriction (FGR) is a serious pregnancy complication affecting ∼8% of all pregnancies. There is no treatment to increase fetal growth in the uterus. Gene therapy presents a promising treatment strategy for FGR, with the use of adenoviral vectors encoding for proteins such as vascular endothelial growth factor (VEGF) and insulin-like growth factor demonstrating improvements in fetal growth, placental function, and neonatal outcome in preclinical studies. Safety assessments suggest no adverse risk to the mother or fetus for VEGF maternal gene therapy; a clinical trial is in development. This review assesses research into placenta-directed gene therapy for FGR, investigating the use of transgenes and vectors, their route of administration in obstetrics, and the steps that will be needed to take this treatment modality into the clinic.

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Section: What Is Gene Therapy? (B)mentioning

confidence: 99%

Placenta-directed gene therapy for fetal growth restriction

Krishnan

David

2017

Seminars in Fetal and Neonatal Medicine

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“…This technique, called therapeutic angiogenesis, has been trialed extensively for coronary artery ischaemia and is now reaching phase 3 trials. 82 Studies in large and small FGR animal models have confirmed the efficacy of this approach for improving fetal growth before birth. In normal sheep pregnancy, injection of Ad.VEGF (1 Â 10 11 particles), compared with injection of a control nonvasoactive vector, increased uterine artery volume blood flow within 7 days of injection, and long term, this increase in flow persisted for at least 4 weeks until the end of gestation.…”

Section: Maternal Vegf Gene Therapymentioning

confidence: 95%

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction

Groom

David

2018

American Journal of Obstetrics and Gynecology

130

101

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Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology. This renders the study findings less reliable for determining clinical significance. For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0.90, 95% confidence interval, 0.81-1.00) and that a dose of ≥100 mg should be recommended and to start at or before 16 weeks of gestation. These findings support national clinical practice guidelines. In vitro and in vivo studies suggest that low-molecular-weight heparin may prevent fetal growth restriction; however, evidence from randomized control trials is inconsistent. A meta-analysis of multicenter trial data does not demonstrate any positive preventative effect of low-molecular-weight heparin on a primary composite outcome of placenta-mediated complications including fetal growth restriction (18% vs 18%; absolute risk difference, 0.6%; 95% confidence interval, 10.4-9.2); use of low-molecular-weight heparin for the prevention of fetal growth restriction should remain in the research setting. There are even fewer treatment options once fetal growth restriction is diagnosed. At present the only management option if the risk of hypoxia, acidosis, and intrauterine death is high is iatrogenic preterm birth, with the use of peripartum maternal administration of magnesium sulphate for neuroprotection and corticosteroids for fetal lung maturity, to prevent adverse neonatal outcomes. The pipeline of potential therapies use different strategies, many aiming to increase fetal growth by improving poor placentation and uterine blood flow. Phosphodiesterase type 5 inhibitors that potentiate nitric oxide availability such as sildenafil citrate have been extensively researched both in preclinical and clinical studies; results from the Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction consortium of randomized control clinical trials are keenly awaited. Targeting the uteroplacental circulation with novel therapeutics is another approach, the most advanced being maternal vascular endothelial growth factor gene therapy, which is being translated into the clinic via the doEs Vascular endothelial growth factor gene therapy safEly impRove outcome in seveRe Early-onset fetal growth reSTriction co...

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“…Действительно, микропузырьки играют решающую роль в защите и транспорте эндогенных мРНК и уже были использованы для доставки синтетических, терапевтических мРНК (таких, как мРНК-21) [86]. Другими средствами доставки либо пре-мРНК (для повышения уровня мРНК) или противосмысловых мРНК (для снижения уровня мРНК) могут служить вирусы, предназначенные для генной терапии (такие как лентивирусы или адено-ассоциированные вирусы) [87]. Перспективными могут быть разработки и в области нанотехнологий; например, наночастицы золота со средним диаметром 13 нм были функционализированы монослоем алкилтиол-модифицированных двухцепочечных молекул РНК [88].…”

Section: заключениеunclassified

MicroRNA in ischemic stroke

Айтбаев¹,

Муркамилов

Fоmin

et al. 2018

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Today, stroke is the third most common pathology after cardiovascular disease and cancer, as well as the leading cause of disability in the world. Although some progress has been made in the field of primary and secondary stroke prevention over the past few decades, a deeper knowledge of the pathophysiology of the disease is needed to significantly improve diagnosis and therapy. MicroRNA (miRNA) is an important, recently identified class of posttranscriptional regulators of gene expression. MiRNA can be used as a tool for therapeutic interventions. This review considers a role of miRNAs in the regulation of experimental stroke and in the development of carotid artery stroke. A potential role of miRNAs as promising biomarkers of stroke is discussed.

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Recent Advancements in Cardiovascular Gene Therapy and Vascular Biology

Cited by 21 publications

References 65 publications

Placenta-directed gene therapy for fetal growth restriction

Placenta-directed gene therapy for fetal growth restriction

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction

MicroRNA in ischemic stroke

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