Phase i study of multi-gene cell therapy in patients with peripheral artery disease

P. Michael Grossman*, Emile R. Mohler, Blake J. Roessler, Robert L. Wilensky, Bruce L. Levine, Edward Y. Woo, Gilbert R. Upchurch, Jacob Schneiderman, Belly Koren, Marina Hutoran, Diana Gershstein, Moshe Y. Flugelman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Alternative treatment strategies for claudication are needed and cell-based therapies designed to induce angiogenesis are promising. The purpose of this report was to conduct a Phase I safety, dose-escalating, non-randomized, open-label study of autologous, fully differentiated venous endothelial and smooth muscle cells called MultiGeneAngio (MGA) for claudication due to peripheral artery disease. Twelve subjects, at two centers, received a single intra-arterial infusion of a suspension of equal amounts of transduced autologous venous smooth muscle cells expressing vascular endothelial growth factor (VEGF165) and endothelial cells expressing angiopoietin-1 (Ang-1) (Cohort 1: 1 × 107, Cohort 2: 2 × 107, Cohort 3: 5 × 107, Cohort 4: 7 × 107). The treatment was given unblinded and in the more symptomatic lower extremity. Transduced cells were tested for in vitro doubling time, telomerase activity, and gene expression. The main outcomes were clinical safety and tolerability. Other safety measures included ankle-brachial index (ABI) and walking time on a treadmill. All subjects were male (mean age 60 ± 5 years) including 25% with diabetes mellitus. At 1-year follow-up, there was one serious adverse event possibly related to MGA. Safety endpoints including VEGF and Ang-1 plasma protein levels were within normal ranges in all subjects. The mean maximal walking time increased from baseline to 1 year and the index limb ABI was unchanged, indicating no safety concerns. MGA, an autologous, transduced, cell-based therapy was well tolerated and safe in this Phase I study. Further evaluation is warranted in randomized human studies. Clinical Trial Registration: Identifier: NCT00390767.

Original languageEnglish
Pages (from-to)21-32
Number of pages12
JournalVascular Medicine
Issue number1
StatePublished - 1 Feb 2016
Externally publishedYes


FundersFunder number
National Institutes of Health
National Center for Advancing Translational SciencesUL1TR000433


    • cell therapy
    • claudication
    • peripheral artery disease
    • vascular


    Dive into the research topics of 'Phase i study of multi-gene cell therapy in patients with peripheral artery disease'. Together they form a unique fingerprint.

    Cite this