Gene therapy for diabetic peripheral neuropathy: A randomized, placebo‐controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor

VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The tria...

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Published inClinical and translational science Vol. 14; no. 3; pp. 1176 - 1184
Main Authors Kessler, John A., Shaibani, Aziz, Sang, Christine N., Christiansen, Mark, Kudrow, David, Vinik, Aaron, Shin, Nari
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.05.2021
John Wiley and Sons Inc
Wiley
Subjects
Adverse events
Aged
Clinical trials
Demographics
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
Diabetic Neuropathies - complications
Diabetic Neuropathies - genetics
Diabetic Neuropathies - therapy
Diabetic neuropathy
DNA
Double-Blind Method
Female
Gabapentin
Gene therapy
Gene transfer
Genetic Therapy - methods
Hepatocyte growth factor
Hepatocyte Growth Factor - genetics
Humans
Injections, Intramuscular
Isoforms
Male
Middle Aged
Muscles
Neuralgia - diagnosis
Neuralgia - genetics
Neuralgia - therapy
Pain
Pain Measurement - statistics & numerical data
Peripheral neuropathy
Placebos
Placebos - administration & dosage
Placebos - adverse effects
Plasmids - administration & dosage
Plasmids - adverse effects
Plasmids - genetics
Protein expression
Proteins
Quality of life
Safety
Treatment Outcome
Online AccessGet full text

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Abstract VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3‐1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3‐1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3‐1 was change from baseline in the mean 24‐h Numerical Rating Scale (NRS) pain score. In DPN 3‐1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well‐tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3‐1. In DPN 3‐1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3‐1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3‐1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long‐lasting pain‐relieving effects of VM202 observed in DPN 3‐1b warrant another rigorous phase III study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN. WHAT QUESTION DID THIS STUDY ADDRESS? Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Nonviral gene therapy can be used safely and practically to treat DPN. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.
AbstractList VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3‐1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3‐1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3‐1 was change from baseline in the mean 24‐h Numerical Rating Scale (NRS) pain score. In DPN 3‐1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well‐tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3‐1. In DPN 3‐1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3‐1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3‐1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long‐lasting pain‐relieving effects of VM202 observed in DPN 3‐1b warrant another rigorous phase III study.Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN.WHAT QUESTION DID THIS STUDY ADDRESS?Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder?WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?Nonviral gene therapy can be used safely and practically to treat DPN.HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.
Abstract VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3‐1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3‐1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3‐1 was change from baseline in the mean 24‐h Numerical Rating Scale (NRS) pain score. In DPN 3‐1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well‐tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3‐1. In DPN 3‐1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3‐1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3‐1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long‐lasting pain‐relieving effects of VM202 observed in DPN 3‐1b warrant another rigorous phase III study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN. WHAT QUESTION DID THIS STUDY ADDRESS? Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Nonviral gene therapy can be used safely and practically to treat DPN. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.
VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3-1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3-1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3-1 was change from baseline in the mean 24-h Numerical Rating Scale (NRS) pain score. In DPN 3-1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well-tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3-1. In DPN 3-1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3-1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3-1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long-lasting pain-relieving effects of VM202 observed in DPN 3-1b warrant another rigorous phase III study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN. WHAT QUESTION DID THIS STUDY ADDRESS? Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Nonviral gene therapy can be used safely and practically to treat DPN. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.
VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3-1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3-1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3-1 was change from baseline in the mean 24-h Numerical Rating Scale (NRS) pain score. In DPN 3-1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well-tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3-1. In DPN 3-1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3-1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3-1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long-lasting pain-relieving effects of VM202 observed in DPN 3-1b warrant another rigorous phase III study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN. WHAT QUESTION DID THIS STUDY ADDRESS? Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Nonviral gene therapy can be used safely and practically to treat DPN. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3-1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3-1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3-1 was change from baseline in the mean 24-h Numerical Rating Scale (NRS) pain score. In DPN 3-1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well-tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3-1. In DPN 3-1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3-1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3-1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long-lasting pain-relieving effects of VM202 observed in DPN 3-1b warrant another rigorous phase III study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN. WHAT QUESTION DID THIS STUDY ADDRESS? Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Nonviral gene therapy can be used safely and practically to treat DPN. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.
VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9 months (DPN 3‐1) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12 months (DPN 3‐1b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3‐1 was change from baseline in the mean 24‐h Numerical Rating Scale (NRS) pain score. In DPN 3‐1b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well‐tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3‐1. In DPN 3‐1b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3‐1b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3‐1b, symptomatic relief was maintained for 8 months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long‐lasting pain‐relieving effects of VM202 observed in DPN 3‐1b warrant another rigorous phase III study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN. WHAT QUESTION DID THIS STUDY ADDRESS? Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Nonviral gene therapy can be used safely and practically to treat DPN. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.
Author Christiansen, Mark
Sang, Christine N.
Shaibani, Aziz
Vinik, Aaron
Kessler, John A.
Shin, Nari
Kudrow, David
AuthorAffiliation 5 Neurological Research Institute Santa Monica California USA
2 Nerve and Muscle Center of Texas Texas Medical Center Houston Texas USA
3 Department of Neurology Brigham and Women's Hospital Boston Massachusetts USA
4 Diablo Clinical Research Center Walnut Creek California USA
7 Helixmith Inc Seoul Korea
6 Strelitz Diabetes Center Eastern Virginia Medical School Norfolk Virginia USA
1 Department of Neurology Northwestern University Chicago Illinois USA
AuthorAffiliation_xml – name: 4 Diablo Clinical Research Center Walnut Creek California USA
– name: 3 Department of Neurology Brigham and Women's Hospital Boston Massachusetts USA
– name: 6 Strelitz Diabetes Center Eastern Virginia Medical School Norfolk Virginia USA
– name: 2 Nerve and Muscle Center of Texas Texas Medical Center Houston Texas USA
– name: 7 Helixmith Inc Seoul Korea
– name: 1 Department of Neurology Northwestern University Chicago Illinois USA
– name: 5 Neurological Research Institute Santa Monica California USA
Author_xml – sequence: 1
  givenname: John A.
  surname: Kessler
  fullname: Kessler, John A.
  email: jakessler@northwestern.edu
  organization: Northwestern University
– sequence: 2
  givenname: Aziz
  surname: Shaibani
  fullname: Shaibani, Aziz
  organization: Texas Medical Center
– sequence: 3
  givenname: Christine N.
  surname: Sang
  fullname: Sang, Christine N.
  organization: Brigham and Women's Hospital
– sequence: 4
  givenname: Mark
  surname: Christiansen
  fullname: Christiansen, Mark
  organization: Diablo Clinical Research Center
– sequence: 5
  givenname: David
  surname: Kudrow
  fullname: Kudrow, David
  organization: Neurological Research Institute
– sequence: 6
  givenname: Aaron
  surname: Vinik
  fullname: Vinik, Aaron
  organization: Eastern Virginia Medical School
– sequence: 7
  givenname: Nari
  surname: Shin
  fullname: Shin, Nari
  organization: Helixmith Inc
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33465273$$D View this record in MEDLINE/PubMed
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Cites_doi 10.2337/dc05-2228
10.1006/bbrc.2001.4819
10.1136/bjo.84.7.732
10.1038/gt.2010.101
10.1016/j.mcn.2004.07.007
10.1073/pnas.91.10.4357
10.1097/00001756-200105250-00022
10.1161/hc4401.098470
10.1523/JNEUROSCI.2919-10.2010
10.1001/jamaneurol.2017.0486
10.1016/j.bbrc.2018.08.054
10.1038/mt.2008.214
10.1161/01.HYP.0000046919.41112.4B
10.1152/ajpheart.00280.2008
10.1016/j.hepres.2004.09.002
10.1016/j.ecl.2013.06.001
10.1148/radiol.2483071579
10.1161/01.HYP.33.6.1379
10.1097/AJP.0000000000000124
10.1186/1742-2094-11-92
10.1080/21678421.2016.1259334
10.1038/sj.gt.3301379
10.1038/gt.2012.87
10.1523/JNEUROSCI.3135-10.2010
10.1016/j.neures.2005.04.004
10.1101/gad.11.24.3341
10.1523/JNEUROSCI.18-20-08369.1998
10.1038/mt.2013.69
10.1096/fj.201800476R
10.1161/01.CIR.0000012146.07240.FD
10.1038/gt.2011.21
10.1089/pop.2008.0015
10.1074/jbc.272.8.5187
10.1016/S0896-6273(00)80247-0
10.1038/gt.2015.110
10.1002/acn3.186
10.1038/s41598-018-26704-x
10.1111/j.1526-4637.2011.01120.x
10.1212/01.wnl.0000259085.61898.9e
10.1016/j.cardfail.2011.03.004
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CorporateAuthor the VM202 study group
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Notes VM202 Study Group (in alphabetical order): Senda Ajroud‐Driss, Jeffrey Allen, Victor Biton, Michael Bowman, Thomas Brannagan, Joe Chehade, Richard S. Cherlin, Mazen Dimachkie, Joseph S. Gimbel, Maria Kasper, Leslie Klaff, Lon D. Lynn, Alexander Reyzelman, Rob Singleton, Elias Siraj, Thomas Toothaker, Miguel Trevino, Judith L White, James Wymer, Douglas Young, Tomasz Ziedalski.
Funding information
Helixmith Inc. provided funding for Aziz Shaibani, Christine Sang, Mark Christiansen, David Kudrow, Aaron Vinik, and Nari Shin. Helixmith paid the costs of performing the trial and paid the salary of the statistician, Nari Shin.
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Wiley
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References 2015; 13
2015; 2
1993; 68
2001; 283
1996; 17
1992; 263
2013; 21
2004; 27
1997; 272
2010; 17
2018; 503
2015; 31
2013; 42
2013; 20
2008; 249
2008; 11
2011; 12
2011; 17
2011; 18
2014; 21
2011; 104
1998; 18
2004; 30
2017; 74
2018; 8
1997; 11
2001; 8
2005; 52
2000; 84
2006; 29
1999; 33
2002; 105
2017; 18
2001; 12
1994; 91
2018; 32
2003; 41
2007; 68
2010; 30
2008; 295
2016; 23
2009; 17
e_1_2_7_6_1
e_1_2_7_5_1
e_1_2_7_4_1
e_1_2_7_3_1
e_1_2_7_9_1
e_1_2_7_7_1
e_1_2_7_19_1
e_1_2_7_18_1
e_1_2_7_17_1
e_1_2_7_16_1
e_1_2_7_40_1
e_1_2_7_2_1
e_1_2_7_15_1
e_1_2_7_41_1
e_1_2_7_14_1
e_1_2_7_42_1
e_1_2_7_13_1
e_1_2_7_43_1
e_1_2_7_12_1
e_1_2_7_44_1
e_1_2_7_11_1
e_1_2_7_10_1
e_1_2_7_26_1
e_1_2_7_27_1
e_1_2_7_28_1
e_1_2_7_30_1
e_1_2_7_25_1
e_1_2_7_31_1
Guedon JM (e_1_2_7_8_1) 2015; 13
e_1_2_7_24_1
e_1_2_7_23_1
e_1_2_7_33_1
e_1_2_7_22_1
e_1_2_7_34_1
e_1_2_7_21_1
Liu KX (e_1_2_7_32_1) 1992; 263
e_1_2_7_35_1
e_1_2_7_20_1
e_1_2_7_36_1
e_1_2_7_37_1
e_1_2_7_38_1
e_1_2_7_39_1
Appasamy R (e_1_2_7_29_1) 1993; 68
References_xml – volume: 30
  start-page: 14735
  year: 2010
  end-page: 14744
  article-title: Dynamic plasticity of axons within a cutaneous milieu
  publication-title: J Neurosci
– volume: 68
  start-page: 270
  issue: 3
  year: 1993
  end-page: 276
  article-title: Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats
  publication-title: Lab Invest
– volume: 20
  start-page: 717
  issue: 7
  year: 2013
  end-page: 722
  article-title: Kim K‐B Intramyocardial transfer of hepatocyte growth factor as an adjunct to CABG: phase I clinical study
  publication-title: Gene Ther
– volume: 41
  start-page: 88
  issue: 1
  year: 2003
  end-page: 92
  article-title: Hepatocyte growth factor and left ventricular geometry in end‐stage renal disease
  publication-title: Hypertension
– volume: 68
  start-page: 1178
  year: 2007
  end-page: 1182
  article-title: The impact of neuropathic pain on health‐related quality of life: review and implications
  publication-title: Neurology
– volume: 42
  start-page: 747
  year: 2013
  end-page: 787
  article-title: Diabetic neuropathy
  publication-title: Endocrinol Metab Clin North Am
– volume: 91
  start-page: 4357
  issue: 10
  year: 1994
  end-page: 4361
  article-title: Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice
  publication-title: Proc Natl Acad Sci USA
– volume: 17
  start-page: 1157
  year: 1996
  end-page: 1172
  article-title: Hepatocyte growth factor scatter factor is an axonal chemoattractant and a neurotrophic factor for spinal motor neurons
  publication-title: Neuron
– volume: 18
  start-page: 788
  issue: 8
  year: 2011
  end-page: 794
  article-title: Safety of a non‐viral plasmid‐encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study
  publication-title: Gene Ther
– volume: 21
  start-page: 92
  issue: 11
  year: 2014
  article-title: Improvement of spinal non‐viral IL‐10 gene delivery by D‐mannose as a transgene adjuvant to control chronic neuropathic pain
  publication-title: J Neuroinflammation
– volume: 18
  start-page: 8369
  issue: 20
  year: 1998
  end-page: 8381
  article-title: Autocrine hepatocyte growth factor provides a local mechanism for promoting axonal growth
  publication-title: J Neurosci
– volume: 17
  start-page: 42
  issue: 1
  year: 2009
  end-page: 50
  article-title: Nonviral retrograde gene transfer of human hepatocyte growth factor improves neuropathic pain‐related phenomena in rats
  publication-title: Mol Ther
– volume: 11
  start-page: 317
  year: 2008
  end-page: 328
  article-title: Painful diabetic peripheral neuropathy in a managed care setting: patient identification, prevalence estimates, and pharmacy utilization patterns
  publication-title: Population Health Manage
– volume: 249
  start-page: 107
  issue: 1
  year: 2008
  end-page: 118
  article-title: MR assessment of myocardial perfusion, viability, and function after intramyocardial transfer of VM202, a new plasmid human hepatocyte growth factor in ischemic swine myocardium
  publication-title: Radiology
– volume: 283
  start-page: 606
  year: 2001
  end-page: 612
  article-title: Identification of HGF‐like protein as a novel neurotrophic factor for avian dorsal root ganglion sensory neurons
  publication-title: Biochem Biophys Res Commun
– volume: 30
  start-page: 12414
  year: 2010
  end-page: 12423
  article-title: Hepatocyte growth factor‐Met signaling is required for Runx1 extinction and peptidergic differentiation in primary nociceptive neurons
  publication-title: J Neurosci
– volume: 13
  start-page: 27
  issue: 11
  year: 2015
  article-title: Current gene therapy using viral vectors for chronic pain
  publication-title: Mol Pain
– volume: 104
  start-page: 2344
  issue: 19
  year: 2011
  end-page: 2350
  article-title: Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes
  publication-title: Circulation
– volume: 23
  start-page: 306
  issue: 3
  year: 2016
  end-page: 312
  article-title: Perin EC Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia
  publication-title: Gene Ther
– volume: 272
  start-page: 5187
  issue: 8
  year: 1997
  end-page: 5191
  article-title: Hepatocyte growth factor promotes motor neuron survival and synergizes with ciliary neurotrophic factor
  publication-title: J Biol Chem
– volume: 12
  start-page: 1403
  year: 2001
  end-page: 1407
  article-title: Expression of HGF and cMet in the peripheral nervous system of adult rats following sciatic nerve injury
  publication-title: NeuroReport
– volume: 17
  start-page: 1442
  year: 2010
  end-page: 1452
  article-title: Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia
  publication-title: Gene Ther
– volume: 8
  start-page: 8316
  issue: 1
  year: 2018
  article-title: Hepatocyte growth factor (HGF) promotes peripheral nerve regeneration by activating repair schwann cells
  publication-title: Sci Rep
– volume: 33
  start-page: 1379
  year: 1999
  end-page: 1384
  article-title: Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy
  publication-title: Hypertension
– volume: 21
  start-page: 1279
  issue: 6
  year: 2013
  end-page: 1286
  article-title: Phase 1/2 open‐label dose‐escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy
  publication-title: Mol Ther
– volume: 30
  start-page: 175
  issue: 3
  year: 2004
  end-page: 181
  article-title: Pharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein
  publication-title: Hepatol Res
– volume: 74
  start-page: 773
  issue: 7
  year: 2017
  end-page: 779
  article-title: Association of long‐term opioid therapy with functional status, adverse outcomes, and mortality among patients with polyneuropathy
  publication-title: JAMA Neurol
– volume: 27
  start-page: 441
  issue: 4
  year: 2004
  end-page: 452
  article-title: HGF promotes survival and growth of maturing sympathetic neurons by PI‐3 kinase‐ and MAP kinase‐dependent mechanisms
  publication-title: Mol Cell Neurosci
– volume: 52
  start-page: 299
  year: 2005
  end-page: 310
  article-title: Nonviral HVJ (hemagglutinating virus of Japan) liposome‐mediated retrograde gene transfer of human hepatocyte growth factor into rat nervous system promotes functional and histological recovery of the crushed nerve
  publication-title: Neurosci Res
– volume: 105
  start-page: 1491
  year: 2002
  end-page: 1496
  article-title: Impairment of collateral formation in lipoprotein(a) transgenic mice: therapeutic angiogenesis induced by human hepatocyte growth factor gene
  publication-title: Circulation
– volume: 29
  start-page: 1518
  year: 2006
  end-page: 1522
  article-title: The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes
  publication-title: Diabetes Care
– volume: 503
  start-page: 2855
  year: 2018
  end-page: 2860
  article-title: c‐Fos is necessary for HGF‐mediated gene regulation and cell migration in Schwann cells
  publication-title: BBRC
– volume: 12
  start-page: 808
  issue: 5
  year: 2011
  end-page: 822
  article-title: Gene therapy for chronic neuropathic pain: how does it work and where do we stand today?
  publication-title: Pain Med
– volume: 295
  start-page: H522
  issue: 2
  year: 2008
  end-page: H532
  article-title: Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium
  publication-title: Am J Physiol Heart Circ Physiol
– volume: 31
  start-page: 414
  issue: 5
  year: 2015
  end-page: 424
  article-title: Opioid use in the management of diabetic peripheral neuropathy (DPN) in a large commercially insured population
  publication-title: Clin J Pain
– volume: 2
  start-page: 465
  issue: 5
  year: 2015
  end-page: 478
  article-title: Double‐blind, placebo‐controlled study of HGF gene therapy in diabetic neuropathy
  publication-title: Ann Clin Transl Neurol
– volume: 11
  start-page: 3341
  year: 1997
  end-page: 3350
  article-title: Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons
  publication-title: Genes Dev
– volume: 18
  start-page: 269
  issue: 3–4
  year: 2017
  end-page: 278
  article-title: Open label study to assess the safety of VM202 in subjects with amyotrophic lateral sclerosis
  publication-title: Amyotroph Lateral Scler Frontotemporal Degener
– volume: 263
  start-page: G642
  issue: 5 Pt 1
  year: 1992
  end-page: G649
  article-title: Importance of the liver in plasma clearance of hepatocyte growth factors in rats
  publication-title: Am J Physiol
– volume: 84
  start-page: 732
  issue: 7
  year: 2000
  end-page: 735
  article-title: Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy
  publication-title: Br J Ophthalmol
– volume: 32
  start-page: 5119
  issue: 9
  year: 2018
  end-page: 5131
  article-title: Effective control of neuropathic pain by transient expression of hepatocyte growth factor in a mouse chronic constriction injury model
  publication-title: FASEB J
– volume: 17
  start-page: 601
  issue: 7
  year: 2011
  end-page: 611
  article-title: Human hepatocyte growth factor (VM202) gene therapy via transendocardial injection in a pig model of chronic myocardial ischemia
  publication-title: J Card Fail
– volume: 8
  start-page: 181
  year: 2001
  end-page: 189
  article-title: Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease
  publication-title: Gene Ther
– ident: e_1_2_7_2_1
  doi: 10.2337/dc05-2228
– ident: e_1_2_7_16_1
  doi: 10.1006/bbrc.2001.4819
– ident: e_1_2_7_42_1
  doi: 10.1136/bjo.84.7.732
– ident: e_1_2_7_13_1
  doi: 10.1038/gt.2010.101
– ident: e_1_2_7_22_1
  doi: 10.1016/j.mcn.2004.07.007
– ident: e_1_2_7_31_1
  doi: 10.1073/pnas.91.10.4357
– ident: e_1_2_7_18_1
  doi: 10.1097/00001756-200105250-00022
– ident: e_1_2_7_28_1
  doi: 10.1161/hc4401.098470
– ident: e_1_2_7_14_1
  doi: 10.1523/JNEUROSCI.2919-10.2010
– ident: e_1_2_7_6_1
  doi: 10.1001/jamaneurol.2017.0486
– ident: e_1_2_7_44_1
  doi: 10.1016/j.bbrc.2018.08.054
– ident: e_1_2_7_12_1
  doi: 10.1038/mt.2008.214
– ident: e_1_2_7_43_1
  doi: 10.1161/01.HYP.0000046919.41112.4B
– ident: e_1_2_7_34_1
  doi: 10.1152/ajpheart.00280.2008
– ident: e_1_2_7_30_1
  doi: 10.1016/j.hepres.2004.09.002
– ident: e_1_2_7_4_1
  doi: 10.1016/j.ecl.2013.06.001
– volume: 263
  start-page: G642
  issue: 5
  year: 1992
  ident: e_1_2_7_32_1
  article-title: Importance of the liver in plasma clearance of hepatocyte growth factors in rats
  publication-title: Am J Physiol
– ident: e_1_2_7_40_1
  doi: 10.1148/radiol.2483071579
– ident: e_1_2_7_25_1
  doi: 10.1161/01.HYP.33.6.1379
– ident: e_1_2_7_7_1
  doi: 10.1097/AJP.0000000000000124
– ident: e_1_2_7_10_1
  doi: 10.1186/1742-2094-11-92
– volume: 68
  start-page: 270
  issue: 3
  year: 1993
  ident: e_1_2_7_29_1
  article-title: Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats
  publication-title: Lab Invest
– ident: e_1_2_7_41_1
  doi: 10.1080/21678421.2016.1259334
– ident: e_1_2_7_27_1
  doi: 10.1038/sj.gt.3301379
– ident: e_1_2_7_37_1
  doi: 10.1038/gt.2012.87
– ident: e_1_2_7_17_1
  doi: 10.1523/JNEUROSCI.3135-10.2010
– volume: 13
  start-page: 27
  issue: 11
  year: 2015
  ident: e_1_2_7_8_1
  article-title: Current gene therapy using viral vectors for chronic pain
  publication-title: Mol Pain
– ident: e_1_2_7_19_1
  doi: 10.1016/j.neures.2005.04.004
– ident: e_1_2_7_21_1
  doi: 10.1101/gad.11.24.3341
– ident: e_1_2_7_24_1
  doi: 10.1523/JNEUROSCI.18-20-08369.1998
– ident: e_1_2_7_33_1
  doi: 10.1038/mt.2013.69
– ident: e_1_2_7_38_1
  doi: 10.1096/fj.201800476R
– ident: e_1_2_7_26_1
  doi: 10.1161/01.CIR.0000012146.07240.FD
– ident: e_1_2_7_35_1
  doi: 10.1038/gt.2011.21
– ident: e_1_2_7_5_1
  doi: 10.1089/pop.2008.0015
– ident: e_1_2_7_23_1
  doi: 10.1074/jbc.272.8.5187
– ident: e_1_2_7_15_1
  doi: 10.1016/S0896-6273(00)80247-0
– ident: e_1_2_7_36_1
  doi: 10.1038/gt.2015.110
– ident: e_1_2_7_11_1
  doi: 10.1002/acn3.186
– ident: e_1_2_7_20_1
  doi: 10.1038/s41598-018-26704-x
– ident: e_1_2_7_9_1
  doi: 10.1111/j.1526-4637.2011.01120.x
– ident: e_1_2_7_3_1
  doi: 10.1212/01.wnl.0000259085.61898.9e
– ident: e_1_2_7_39_1
  doi: 10.1016/j.cardfail.2011.03.004
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Snippet VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral...
Abstract VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral...
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StartPage 1176
SubjectTerms Adverse events
Aged
Clinical trials
Demographics
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
Diabetic Neuropathies - complications
Diabetic Neuropathies - genetics
Diabetic Neuropathies - therapy
Diabetic neuropathy
DNA
Double-Blind Method
Female
Gabapentin
Gene therapy
Gene transfer
Genetic Therapy - methods
Hepatocyte growth factor
Hepatocyte Growth Factor - genetics
Humans
Injections, Intramuscular
Isoforms
Male
Middle Aged
Muscles
Neuralgia - diagnosis
Neuralgia - genetics
Neuralgia - therapy
Pain
Pain Measurement - statistics & numerical data
Peripheral neuropathy
Placebos
Placebos - administration & dosage
Placebos - adverse effects
Plasmids - administration & dosage
Plasmids - adverse effects
Plasmids - genetics
Protein expression
Proteins
Quality of life
Safety
Treatment Outcome
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Title Gene therapy for diabetic peripheral neuropathy: A randomized, placebo‐controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fcts.12977
https://www.ncbi.nlm.nih.gov/pubmed/33465273
https://www.proquest.com/docview/2542343011
https://www.proquest.com/docview/2479419226
https://pubmed.ncbi.nlm.nih.gov/PMC8212761
https://doaj.org/article/2329437b42c343839e9410cee955d372
Volume 14
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