Phase I study of multi-gene cell therapy in patients with peripheral artery disease.
Vasc Med
; 21(1): 21-32, 2016 Feb.
Article
in En
| MEDLINE
| ID: mdl-26584888
ABSTRACT
UNLABELLED 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 × 10(7), Cohort 2 2 × 10(7), Cohort 3 5 × 10(7), Cohort 4 7 × 10(7)). 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 ClinicalTrials.gov Identifier NCT00390767.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Therapy
/
Cell Transplantation
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Neovascularization, Physiologic
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Myocytes, Smooth Muscle
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Endothelial Cells
/
Angiogenic Proteins
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Peripheral Arterial Disease
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Intermittent Claudication
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Country/Region as subject:
America do norte
Language:
En
Journal:
Vasc Med
Journal subject:
ANGIOLOGIA
Year:
2016
Type:
Article
Affiliation country:
United States