New application of CELLECTRA® electroporation technology dramatically enhances ability of DNA therapy to stimulate blood vessel growth and recovery from debilitation caused by blocked arteries of the legs
Results published in peer-reviewed Journal of Vascular Surgery
BLUE BELL, PA, USA I July 18, 2013 I Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that the use of its proprietary electroporation technology significantly enhanced the ability of a DNA therapy to stimulate blood vessel growth, which may be beneficial for the treatment of critical limb ischemia (CLI) and other forms of peripheral arterial disease (PAD). CLI’s severe blockage of arteries of the lower extremities markedly reduces blood flow, resulting in notable medical impacts and death. In a mouse model, delivery of a synthetically optimized hypoxia-inducible factor-1 alpha (HIF-1α) gene using Inovio’s CELLECTRA® electroporation delivery technology produced significant growth of new blood vessels and improved limb blood flow, limb function recovery, and survival from limb necrosis and amputation. The results were published in a paper entitled, “In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia,” in the peer-reviewed Journal of Vascular Surgery.
Finding an effective therapy for PAD and CLI is imperative because the current standard of care relies primarily on palliative drugs and amputation. PAD affects 8 – 12 million Americans and is associated with a 20 – 30% risk of cardiovascular death within five years. CLI is a more severe stage of PAD affecting over one million people in the US. Up to 20% of CLI patients will die within 12 months of diagnosis; the five-year mortality rate exceeds 70%. The disease is characterized by ischemic rest pain—severe pain in the legs and feet while a person is not moving—or non-healing sores on the feet or legs as well as gangrene. Major limb amputation occurs in up to 40 – 50% of CLI patients within 12 months of diagnosis.
Dr. J. Joseph Kim, Inovio’s president and CEO, said: “We have tremendous momentum and clinical data in achieving best-in-class immune responses with our SynCon® DNA vaccines delivered using our CELLECTRA electroporation system. Others have attempted to treat PAD using angiogenic growth factor DNA therapies without success. This study shows that combining our synthetic gene optimization techniques with our proprietary delivery systems could lead to an effective therapy. While early, this new application in treating PAD and other major chronic diseases offers Inovio a promising therapeutic avenue and additional commercial opportunity.”
In this study, the gene sequence for HIF-1α was synthetically optimized to enhance expression of the growth factor. This DNA therapy was then delivered using Inovio’s CELLECTRA constant current electroporation device, which has been shown to enhance the delivery of DNA plasmids by a 1000 fold using a millisecond pulse. A total of 39 mice were divided into 3 groups: (1) one group receiving HIF-1α DNA delivered with electroporation (EP) (n=13); (2) one group receiving HIF-1α DNA without EP (n=14) and (3) one group receiving a control empty plasmid (pVAX) delivered with EP (n=12). The left femoral artery in each mouse was tied up surgically to simulate an arterial blockage. The right legs were not treated and served as internal controls. The mice were then observed and scored for their limb function. Blood flow in their legs was measured by laser Doppler perfusion imaging.
The results demonstrated that EP delivery of synthetically optimized HIF-1α plasmid DNA significantly improved blood flow in the left hind legs and reduced necrosis (premature cell death) in a mouse model of hind limb ischemia when compared to the results from the two control groups. The treatment also improved survival from severe limb damage and amputation, reduced tissue damage, and increased the number of new capillaries and formation of larger collateral vessels.
About Inovio Pharmaceuticals, Inc.
Inovio is revolutionizing vaccines to prevent and treat today’s cancers and challenging infectious diseases. Its synthetic consensus design approach is intended to help the immune system identify and fight cancer cells or multiple unmatched strains of a mutating virus. These proprietary synthetic vaccines, in combination with Inovio’s electroporation delivery, have in humans generated best-in-class immune responses with a favorable safety profile. Inovio’s lead vaccine, a therapeutic against HPV-caused diseases, is in phase II. Other phase I and preclinical programs focus on HIV, influenza, malaria and hepatitis C virus. Partners and collaborators include the University of Pennsylvania, Merck, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security, University of Manitoba and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.
SOURCE: Inovio Pharmaceuticals
Post Views: 79
New application of CELLECTRA® electroporation technology dramatically enhances ability of DNA therapy to stimulate blood vessel growth and recovery from debilitation caused by blocked arteries of the legs
Results published in peer-reviewed Journal of Vascular Surgery
BLUE BELL, PA, USA I July 18, 2013 I Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that the use of its proprietary electroporation technology significantly enhanced the ability of a DNA therapy to stimulate blood vessel growth, which may be beneficial for the treatment of critical limb ischemia (CLI) and other forms of peripheral arterial disease (PAD). CLI’s severe blockage of arteries of the lower extremities markedly reduces blood flow, resulting in notable medical impacts and death. In a mouse model, delivery of a synthetically optimized hypoxia-inducible factor-1 alpha (HIF-1α) gene using Inovio’s CELLECTRA® electroporation delivery technology produced significant growth of new blood vessels and improved limb blood flow, limb function recovery, and survival from limb necrosis and amputation. The results were published in a paper entitled, “In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia,” in the peer-reviewed Journal of Vascular Surgery.
Finding an effective therapy for PAD and CLI is imperative because the current standard of care relies primarily on palliative drugs and amputation. PAD affects 8 – 12 million Americans and is associated with a 20 – 30% risk of cardiovascular death within five years. CLI is a more severe stage of PAD affecting over one million people in the US. Up to 20% of CLI patients will die within 12 months of diagnosis; the five-year mortality rate exceeds 70%. The disease is characterized by ischemic rest pain—severe pain in the legs and feet while a person is not moving—or non-healing sores on the feet or legs as well as gangrene. Major limb amputation occurs in up to 40 – 50% of CLI patients within 12 months of diagnosis.
Dr. J. Joseph Kim, Inovio’s president and CEO, said: “We have tremendous momentum and clinical data in achieving best-in-class immune responses with our SynCon® DNA vaccines delivered using our CELLECTRA electroporation system. Others have attempted to treat PAD using angiogenic growth factor DNA therapies without success. This study shows that combining our synthetic gene optimization techniques with our proprietary delivery systems could lead to an effective therapy. While early, this new application in treating PAD and other major chronic diseases offers Inovio a promising therapeutic avenue and additional commercial opportunity.”
In this study, the gene sequence for HIF-1α was synthetically optimized to enhance expression of the growth factor. This DNA therapy was then delivered using Inovio’s CELLECTRA constant current electroporation device, which has been shown to enhance the delivery of DNA plasmids by a 1000 fold using a millisecond pulse. A total of 39 mice were divided into 3 groups: (1) one group receiving HIF-1α DNA delivered with electroporation (EP) (n=13); (2) one group receiving HIF-1α DNA without EP (n=14) and (3) one group receiving a control empty plasmid (pVAX) delivered with EP (n=12). The left femoral artery in each mouse was tied up surgically to simulate an arterial blockage. The right legs were not treated and served as internal controls. The mice were then observed and scored for their limb function. Blood flow in their legs was measured by laser Doppler perfusion imaging.
The results demonstrated that EP delivery of synthetically optimized HIF-1α plasmid DNA significantly improved blood flow in the left hind legs and reduced necrosis (premature cell death) in a mouse model of hind limb ischemia when compared to the results from the two control groups. The treatment also improved survival from severe limb damage and amputation, reduced tissue damage, and increased the number of new capillaries and formation of larger collateral vessels.
About Inovio Pharmaceuticals, Inc.
Inovio is revolutionizing vaccines to prevent and treat today’s cancers and challenging infectious diseases. Its synthetic consensus design approach is intended to help the immune system identify and fight cancer cells or multiple unmatched strains of a mutating virus. These proprietary synthetic vaccines, in combination with Inovio’s electroporation delivery, have in humans generated best-in-class immune responses with a favorable safety profile. Inovio’s lead vaccine, a therapeutic against HPV-caused diseases, is in phase II. Other phase I and preclinical programs focus on HIV, influenza, malaria and hepatitis C virus. Partners and collaborators include the University of Pennsylvania, Merck, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security, University of Manitoba and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.
SOURCE: Inovio Pharmaceuticals
Post Views: 79
