pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia

@article{Deev2015pCMVvegf165IG,
  title={pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia},
  author={Roman V. Deev and Ilia Y. Bozo and Nina D. Mzhavanadze and D. A. Voronov and Aleksandr V. Gavrilenko and Yu. V. Chervyakov and Ilia N. Staroverov and Roman E. Kalinin and P G Shvalb and Artur A. Isaev},
  journal={Journal of Cardiovascular Pharmacology and Therapeutics},
  year={2015},
  volume={20},
  pages={473 - 482}
}
  • R. DeevI. Y. Bozo A. Isaev
  • Published 13 March 2015
  • Medicine, Biology
  • Journal of Cardiovascular Pharmacology and Therapeutics
Effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. There are a number of choices available to the vascular surgeon. Open or endovascular revascularization is the treatment of choice when applicable. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression. Therefore, new methods of treatment are needed. We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the… 
View on SAGE
ncbi.nlm.nih.gov
51 Citations
Highly Influential Citations
1
Background Citations
12
Methods Citations
2
Results Citations
1

Figures and Tables from this paper

51 Citations

Results of an International Postmarketing Surveillance Study of pl-VEGF165 Safety and Efficacy in 210 Patients with Peripheral Arterial Disease

Pain-free walking distance (PWD), blood flow linear velocity (BFLV), and ankle-brachial index (ABI) were monitored for 6 months and the greatest therapeutic effect was observed for stage III disease: PWD increased by 683% and the mean value was unchanged in the control group.

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

The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years, and the target limb salvage was 95% and 67% in the pl-VEGF165 and control groups, respectively.

Is gene therapy for limb ischemia a reality?

Only two angiogenic therapy drugs have been approved, one in Russia and another in Japan, which seem a very small number, in view of the large volume of investment made in pre-clinical and clinical studies.

Progress of Gene Therapy in Cardiovascular Disease

The recent advances in proangiogenic gene therapy for critical limb ischemia and DNA vaccine for hypertension are discussed.

Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses

This clinical study describes the intralesional application of the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor (VEGF164) and fibroblast…

Evaluation of long-term treatment results of patients with critical limb ischemia and diabetes mellitus with different management approaches

The optimal management tactic for patients with critical lower limb ischemia and underlying diabetes mellitus is direct revascularizing intervention on the lower limb arteries with additional angiogenic therapy in the postoperative period.

Growth factors for angiogenesis in peripheral arterial disease.

The quality of the evidence is low due to risk of bias and imprecision, however, growth factors may decrease the rate of any limb amputations and the direction and size of effects for growth factors on serious adverse events are uncertain.

Angiogenic gene therapy in cardiovascular diseases: dream or vision?

The concept of angiogenic therapy as a sole treatment is re-evaluated and a combination with regenerative therapies or standard revascularization operations might be needed to improve tissue function and clinical benefits.

The Role of the Stem Cells Therapy in the Peripheral Artery Disease

The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the stem cells therapy in this field, from biomarker to possible therapeutic target.

Terapia gênica de isquemia de membro é uma realidade?

The concept of angiogenic therapy emerged in the early 1990s. The method employs genes that encode growth factors to promote formation of new vessels and remodeling of collateral vessels. Since the…
...

References

SHOWING 1-10 OF 25 REFERENCES

Therapeutic Angiogenesis With Intramuscular NV1FGF Improves Amputation-free Survival in Patients With Critical Limb Ischemia.

In patients with CLI, plasmid-based NV1FGF gene transfer was well tolerated, and resulted in a significantly reduced risk of major amputation when compared with placebo, in patients with critical limb ischemia.

Phase I/IIa Clinical Trial of Therapeutic Angiogenesis Using Hepatocyte Growth Factor Gene Transfer to Treat Critical Limb Ischemia

Intramuscular injection of naked HGF plasmid is safe and feasible and can achieve successful improvement of ischemic limbs as sole therapy in patients with critical limb ischemia.

Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia.

Findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA achieves constitutive overexpression of VEGF sufficient to induce therapeutic angiogenesis in selected patients with critical limb ischemia.

Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study

In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.

Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb

Arterial gene transfer of naked DNA for therapeutic angiogenesis: early clinical results.

  • Isner
  • Biology, Medicine
    Advanced drug delivery reviews
  • 1998

[Therapeutic angiogenesis in treatment of patients with chronic obliterating diseases of lower limb arteries].

Using the first Russian gene therapeutic agent Neovasculogen in comprehensive treatment of patients with stage II-III chronic obliterating disease of lower limb arteries according to the Pokrovsky-Fontain classification observed that using the agent was enough for obtaining a persistent satisfactory result preserving for not less than one year.

Human studies of angiogenic gene therapy.

The clinical development of angiogenic gene therapy is examined, several of the lessons learned during the conduct of these trials are summarized, and how this prior experience may guide the Conduct of future preclinical investigations and clinical trials are suggested.

Arterial gene therapy for therapeutic angiogenesis in patients with peripheral artery disease.

There presently is inadequate evidence from published studies to support the routine use of primary pharmacological treatment in patients with critical leg ischemia, and evidence for the utility of medical therapy in the treatment of claudication is no better.

A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel: an initial report of the phase I-IIa study.

  • A. MaruiY. Tabata M. Komeda
  • Medicine, Biology
    Circulation journal : official journal of the Japanese Circulation Society
  • 2007
The sustained release of bFGF from gelatin hydrogel might be simple, safe, and effective to achieve therapeutic angiogenesis because it did not need genetic materials or collection of implanted cells, and because itdid not have any general effects.