Developmental Clinical Studies - Gene Therapy For Vein Graft Failure

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

Failure rates for heart bypass grafts using veins remain very high and represent a major clinical problem that lacks a drug-based treatment. Our prior studies have demonstrated the unique ability of gene therapy (the use of a patient s genes to treat the disease) to prevent the vein getting blocked which is associated with graft failure. We wish to perform a clinical trial in patients undergoing bypass grafting and assess the safety and beneficial effect of gene therapy.

Technical Summary

Our clinical trial application is based on a gene therapy approach for prevention of vein graft failure. The long term failure of bypass grafting using autologous saphenous vein remains a major clinical burden on the NHS. Preventing neointima formation in the immediate time points post-grafting is likely to have a major impact on the frequency of long term graft failure. We have developed a gene therapy approach using a replication-defective adenovirus vector that overexpresses the therapeutic gene ?tissue inhibitor of metalloproteinases-3 (TIMP-3)? that significantly attenuates neointima formation in human saphenous vein ex vivo and pig vein grafts in vivo. We propose a phase I/II clinical trial to assess the safety and efficacy of this approach in patients undergoing elective coronary bypass graft surgery. This first-in-man ex vivo approach maximises target vascular gene transfer while minimising systemic vector dissemination post-grafting. Our trial is designed with key milestones with firm efficacy endpoints.

Publications


10 25 50
 
Description GSK 
Organisation GlaxoSmithKline (GSK)
Department GSK Biologicals SA
Country Belgium, Kingdom of 
Sector Private 
PI Contribution GSK have agreed to partner to make the virus for the trial.
Collaborator Contribution To use their cell line to try and rescue this virus
Impact no outcome yet
Start Year 2016
 
Title AdTimp3 for Gene Therapy 
Description Virus is in stages of GMP production for the implementation of the trial 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2013
Development Status Under active development/distribution
Impact Clinical trial not performed yet. 
 
Description European Researcher Night 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interactive discussion about viruses in cardiovascular disease with a broad range of ages from schoolchildren to adults leading to improved knowledge, further questions and amazing interest

Feedback has been extremely positive
Year(s) Of Engagement Activity 2014
URL http://www.gla.ac.uk/news/headline_341772_en.html
 
Description Glasgow Science Festival 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Schools
Results and Impact A dissemination of information on cardiovascular gene therapy, science and implementation of clinical trial therapies using viruses to school students

n/a
Year(s) Of Engagement Activity 2013
 
Description Glasgow Science Festival 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Schools
Results and Impact We informed the public from children to adults about the concept of using viruses in therapy for cardiovascular disease

Feedback has been extremely positive
Year(s) Of Engagement Activity 2014