Gene therapy for pulmonary hypertension: prospects and challenges

@article{Reynolds2011GeneTF,
  title={Gene therapy for pulmonary hypertension: prospects and challenges},
  author={Paul N Reynolds},
  journal={Expert Opinion on Biological Therapy},
  year={2011},
  volume={11},
  pages={133 - 143}
}
  • P. Reynolds
  • Published 10 January 2011
  • Medicine
  • Expert Opinion on Biological Therapy
Introduction: Recent evidence shows that pulmonary arterial hypertension (PAH) remains a fatal disease despite the introduction of new pharmacological treatments. New options are therefore needed and gene therapy approaches are a rational consideration based on emerging understanding of the genetic basis of PAH. Areas covered: This review briefly discusses the recent developments in clinical management of PAH and the investigation of gene delivery techniques for pulmonary vascular disease from… Expand
Inhaled Gene Transfer for Pulmonary Circulation.
TLDR
A procedure to achieve vector transduction at the distal vasculature in animal models of PH and the methods to evaluate the outcomes of this intervention as a promising new approach in pulmonary vascular diseases are described. Expand
Current and emerging therapeutic approaches to pulmonary hypertension
TLDR
An overview of the current FDA-approved therapies in PAH is provided and the latest promising therapies in preclinical studies such as stem cell-based therapies, gene transfer, and epigenetic therapies are focused on. Expand
Targeted delivery of genes to endothelial cells and cell- and gene-based therapy in pulmonary vascular diseases.
TLDR
Cell-based gene therapy is an approach that augments the therapeutic potential of EPCs and MSCs and may deliver on the promise of reversal of established PAH. Expand
Gene Therapy in Cardiovascular Disease
TLDR
The progress in molecular biology and pharmacogenomics technology could allow for the development of gene containing drugs, which have the potential in the near future to momentously improve the management of a variety of clinical cardiovascular problems. Expand
Genetic Modification of the Lung Directed Toward Treatment of Human Disease.
TLDR
More work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses. Expand
Gene therapy for pulmonary arterial hypertension: is a cure in sight?
  • R. Mathew
  • Medicine
  • Expert opinion on biological therapy
  • 2011
TLDR
The presence of idiopathic PAH in family members suffering from Norrie disease, which is a rare X-linked disease comprised of congenital retinal vasculopathy and other neurological deficits, was showed. Expand
Endothelial nanomedicine for the treatment of pulmonary disease
TLDR
To maximize the chances of creating products that reach patients, nanomedicine engineers and clinicians must work together and use each disease’s need specification to guide the design of practical and effective nanomededicine agents. Expand
Pulmonary arterial hypertension: Advances in pathophysiology and management
TLDR
This article attempts to provide an overview of the etiology, pathophysiology, and current therapeutic modalities in the treatment of PAH. Expand
A recombinant myeloid-binding adenovirus for targeted pulmonary gene therapy
TLDR
Efficient targeting of cell types within the lung may preclude the need for viral modifications that ablate liver sequestration mechanisms, and improve efficacy of Ad5 gene delivery. Expand
Development and Challenges of Nanovectors in Gene Therapy
TLDR
The current state of gene delivery in clinical trials is introduced, and the main goal of gene therapy is to find a gene delivery vehicle that can successfully target diseased cells and deliver therapeutic genes directly to their cellular compartment. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 88 REFERENCES
Cystic fibrosis gene therapy: successes, failures and hopes for the future
TLDR
Current preclinical and clinical research aimed at further developing gene therapy for CF is described and proof-of-principle for gene transfer in the airways is established. Expand
Delivery of DNA to pulmonary endothelium using adenoviral vectors.
Delivery of genes to the pulmonary vascular endothelium is a rational approach for the investigation and potential therapy of pulmonary vascular diseases. Furthermore, in view of the exposure of thisExpand
Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension.
TLDR
Adenoviral vectors containing the BMPR2 gene were developed and delivered to the pulmonary vascular endothelium of rats substantially reduced the pulmonary hypertensive response to chronic hypoxia, as reflected by reductions in pulmonary artery andright ventricular pressures, right ventricular hypertrophy, and muscularization of distal pulmonary arterioles. Expand
Role of apoptosis in pulmonary hypertension: from experimental models to clinical trials.
TLDR
The idea that EC apoptosis may play a central role in the initiation and progression of PAH suggests that therapeutic strategies aimed at endothelial repair and regeneration of ECs may be uniquely effective in the treatment of this disease. Expand
Updated evidence-based treatment algorithm in pulmonary arterial hypertension.
TLDR
Oral anticoagulation is proposed for most patients; diuretic treatment and supplemental oxygen are indicated in cases of fluid retention and hypoxemia, respectively; high doses of calcium-channel blockers are indicated only in the minority of patients who respond to acute vasoreactivity testing. Expand
Genetic Ablation of the Bmpr2 Gene in Pulmonary Endothelium Is Sufficient to Predispose to Pulmonary Arterial Hypertension
TLDR
Investigating whether endothelial Bmpr2 deletion can predispose mice to PAH found that conditional heterozygous or homozygous BmPR2 deletion in pulmonary endothelial cells predisposes mice to develop PAH. Expand
Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation.
TLDR
BMPR2 mutation carriers with PAH present approximately 10 years earlier than noncarriers, with a more severe hemodynamic compromise at diagnosis. Expand
Cell therapy approaches for lung diseases: current status.
TLDR
This review of recent advances in cell therapy with the focus on MSCs and their potential roles in lung development and repair is described. Expand
Pathology of pulmonary arterial hypertension.
  • R. Tuder
  • Medicine
  • Seminars in respiratory and critical care medicine
  • 2009
The pathological features of pulmonary arterial hypertension are highlighted in this review, which can serve as a guide to diagnosis and identification of potential cellular targets for novel linesExpand
Prognosis of pulmonary arterial hypertension: the power of clinical registries of rare diseases.
TLDR
Data from the 2 of the most important present-day registries in PAH give the opportunity to better understand the prognosis of PAH, its determinants, and outcomes in the current treatment era. Expand
...
1
2
3
4
5
...