Vascular endothelial growth factor-induced angiogenic gene therapy in patients with peripheral artery disease.
This phase 1 clinical trial tested the safety of intramuscular gene transfer by using naked plasmid DNA encoding the gene for VEGF, and analyzed the potential therapeutic benefits in patients with severe peripheral arterial disease (PAD). This study was an open-labeled, dose- escalating, single-center trial on nine male patients with severe debilitating PAD who had not responded to conventional therapy. Seven had Buerger's disease and two had arteriosclerosis obliterans. Plasmid DNA (pCK) containing human VEGF165 was given by eight intramuscular injections in and around the area in need of new blood vessels. The study evaluated three escalating total doses (2, 4, and 8 mug of pCK- VEGF165), with half of each total dose given four weeks apart. The follow-up duration was nine months. The gene injections were well tolerated without significant side effects or laboratory abnormalities related to gene transfer. Three patients showed transient edema in their extremities. Ischemic pain of the affected limb was relieved or improved markedly in six of seven patients. Ischemic ulcers healed or improved in four of six patients. The mean ankle-brachial index (ABI) improved significantly. Six of nine patients showed an increase in collateral vessels around the injection sites demonstrated by digital subtraction angiography. However, there was no relationship between the degree of ABI improvement and the dose given. Mean plasma levels of VEGF did not increase significantly. In conclusion, intramuscular injections of pCK- VEGF165 can be performed safely to induce therapeutic angiogenesis in patients with severe PAD.
Kim
Hyun-Joong
HJ
Department of Medicine, Samsung Medical Center, Samsung Biomedical, Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Jang
Shin Yi
SY
Park
Joong-Il
JI
Byun
Jonghoe
J
Kim
Dong-Ik
DI
Do
Young-Soo
YS
Kim
Jong-Mook
JM
Kim
Sunyoung
S
Kim
Byong-Moon
BM
Kim
Won-Bae
WB
Kim
Duk-Kyung
DK
D000328:Adult; D000368:Aged; D015901:Angiography, Digital Subtraction; D001157:Arterial Occlusive Diseases / Q000628:therapy*; D005528:Foot / Q000473:pathology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A