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Long-term safety of intramuscular gene transfer of non-viral FGF1 for peripheral artery disease

Gene Therapy volume 19, pages 264–270 (2012)Cite this article

Abstract

Peripheral artery disease is a progressive disease. Primary ischemic leg symptoms are muscle fatigue, discomfort or pain during ambulation, known as intermittent claudication. The most severe manifestation of peripheral artery disease is critical limb ischemia (CLI). The long-term safety of gene therapy in peripheral artery disease remains unclear. This four center peripheral artery disease registry was designed to evaluate the long-term safety of the intramuscular non-viral fibroblast growth factor-1 (NV1FGF), a plasmid-based angiogenic gene for local expression of fibroblast growth factor-1 versus placebo in patients with peripheral artery disease who had been included in five different phase I and II trials. Here we report a 3-year follow-up in patients suffering from CLI or intermittent claudication. There were 93 evaluable patients, 72 of them in Fontaine stage IV (47 NV1FGF versus 25 placebo) and 21 patients in Fontaine stage IIb peripheral artery disease (15 NV1FGF versus 6 placebo). Safety parameters included rates of non-fatal myocardial infarction (MI), stroke, death, cancer, retinopathy and renal dysfunction. At 3 years, in 93 patients included this registry, there was no increase in retinopathy or renal dysfunction associated with delivery of this angiogenic factor. There was also no difference in the number of strokes, MI or deaths, respectively, for NV1FGF versus placebo. In the CLI group, new cancer occurred in two patients in the NV1FGF group. Conclusions that can be drawn from this relatively small patient group are limited because of the number of patients followed and can only be restricted to safety. Yet, data presented may be valuable concerning rates in cancer, retinopathy, MI or strokes following angiogenesis gene therapy in the absence of any long-term data in angiogenesis gene therapy. It may take several years until data from larger patient populations will become available.

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Acknowledgements

SN is funded by the German Research Foundation (DFG 331/9-1), the Federal Ministry for Education and Research (BMBF 01GN0938), the Interdisciplinary Center for Clinical Research (Nik1/032/08) and the Hans und Gertie Fischer-Stiftung. We thank Marco Heise for his support in data analysis, Edith Siebert for her help in the database and Daniela Kiski to take the initial steps.

Clinical Trial Registration

URL-http://www.clinicaltrials.gov/ct/show/NCT00368797?order=1, Identification number—Talisman 201: NCT00368797, Talisman 211: NCT01157871, PM 202: NCT00798005PM101: NCT01157156, PM 105: NCT01157143 http://clinicaltrials.gov/ct2/show/NCT00798005?term=NV1FGF&rank=1.

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Authors and Affiliations

  1. Department of Cardiology and Angiology, University of M,

    A Niebuhr & S Nikol

  2. ue,

    A Niebuhr & S Nikol

  3. nster, Muenster, Germany

    A Niebuhr & S Nikol

  4. Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, MN, USA

    T Henry & J Goldman

  5. Division of Angiology, Department Heart and Vascular Medicine, University of Bern, Bern, Switzerland

    I Baumgartner

  6. Department of Cardiology B and Hemodynemics, Hôpital Cardiologique, CHRU de Lille, France

    E van Belle

  7. Department of Medical Informatics and Biomathematics, University of Muenster, Muenster, Germany

    J Gerss

  8. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA

    A T Hirsch

  9. Department of Clinical and Interventional Angiology, Asklepios Klinik St Georg, Hamburg, Germany

    S Nikol

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Correspondence to S Nikol.

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Niebuhr, A., Henry, T., Goldman, J. et al. Long-term safety of intramuscular gene transfer of non-viral FGF1 for peripheral artery disease. Gene Ther 19, 264–270 (2012). https://doi.org/10.1038/gt.2011.85

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