Flugelman, Moshe Y.

Grossman, Paul Michael

Levine, Bruce L.

Mohler, Emile

Roessler, Blake J.

Schneiderman, Jacob

Upchurch, Gilbert R.

Wilensky, Robert

Woo, Edward Y.

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Vascular Disease
E2073
JACC March 27, 2012
Volume 59, Issue 13
PHASE I STUDY OF MULTI-GENE CELL THERAPY IN PATIENTS WITH PERIPHERAL ARTERY DISEASE
ACC Moderated Poster Contributions
McCormick Place South, Hall A
Saturday, March 24, 2012, 9:30 a.m.-10:30 a.m.
Session Title: Peripheral Vascular Disease: State of Science II
Abstract Category: 33. Vascular - Pathophysiology - Basic/Angiogenesis/Gene Therapy
Presentation Number: 1121-211
Authors: Paul Michael Grossman, Emile Mohler, Blake J. Roessler, Robert Wilensky, Bruce L. Levine, Edward Y. Woo, Gilbert R. Upchurch, Jacob 
Schneiderman, Moshe Y. Flugelman, University of Michigan Cardiovascular Center, Ann Arbor, MI, USA, University of Pennsylvania, Philadelphia, PA, USA
Background: Treatment options for patients with claudication due to lower extremity (LE) peripheral artery disease (PAD) are limited. Cell based 
therapies designed to induce angiogenesis are promising therapeutics that are intended to reduce pain and improve walking distance. We present the 
one year results of a Phase I safety, dose-escalating, non-randomized open label study, of MultiGeneAngio in subjects with claudication due to LE PAD.
Methods: A total of 12 subjects (4 cohorts of 3 patients each) were enrolled. Subjects received a single intra-arterial infusion of a suspension 
of equal amount of transduced autologous smooth muscle cells expressing vascular endothelial growth factor (VEGF165) and endothelial cells 
expressing Angiopoietin-1 (Ang-1) (Cohort 1 - 1 x 107, Cohort 2 - 2 x 107, Cohort 3 - 5 x 107, Cohort 4 - 7 x 107). The cell suspension was 
administered into the common femoral artery or its main branches proximal to the occlusion site of the more symptomatic LE, as indicated 
by a standardized treadmill test (Gardner protocol). The main outcomes were clinical safety and tolerability of MultiGeneAngio with laboratory 
measurements at specified time intervals compared to the baseline. Other measures included ankle-brachial index (ABI) and maximal walking time 
on treadmill testing.
Results: A total of 12 patients were successfully enrolled at 2 centers. All subjects were male, and their mean age was 60 ± 5 years. Historical 
factors included diabetes (25%), hyperlipidemia (92%), hypertension (92%), CAD (75%), COPD (33%), and smoking history (92%). At the one-year 
post treatment, no serious adverse events (SAEs) related to MultiGeneAngio were observed. Safety endpoints including VEGF and Ang-1 plasma 
protein levels were within normal ranges in all subjects. Mean maximal walking time increased from baseline to 1 year (345 to 533 seconds; p < 
0.05), index limb ABI was unchanged (0.58 to 0.61, p = ns).
Conclusions: MultiGeneAngio, an autologous, transduced, cell based therapy was well tolerated and safe in this phase-1 study. The therapy was 
also associated with increased walking time in these patients with LE claudication. The results of this study warrant further randomized human 
studies.


PHASE I STUDY OF MULTI-GENE CELL THERAPY IN PATIENTS WITH PERIPHERAL ARTERY DISEASE 

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PHASE I STUDY OF MULTI-GENE CELL THERAPY IN PATIENTS WITH PERIPHERAL ARTERY DISEASE

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