Gene Therapy
Gene Therapy
We are contributing to the initial clinical development of therapeutic angiogenesis for the treatment of advanced coronary artery disease under Dr. Matthew Watkins’ leadership. Our efforts focus on intracoronary delivery with the use of amodified viral vector of the gene FGF4 (fibroblast growth factor 4) targeting an angiogenic response in chronic, ischemic myocardium.
The first intracoronary gene therapy treatment in the United States was performed in our center, followed by publication of the report of an initial phase one trial (AGENT I) demonstrating safety and preliminary efficacy of the approach. A second, multi-center investigation has been completed. Results demonstrate a positive impact of treatment with FGF4 on myocardial perfusion. An international phase three trial of therapeutic angiogenesis employing intracoronary FGF4 gene therapy is currently underway. Dr. Watkins serves on the Steering Committee.
Illustration: The amino sequence of recombinant DNA produced t-PA.
Representative Publications
Grines C, Watkins MW, Helmer G, Penny W, Brinker J, Marmur J, West A, Rade JJ, Marrott P, Hammond HK, Engler RL. Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation 2002; 105: 1291-1297.
Grines C, Watkins MW, Mahmarian JJ, Iskandrian AE, Marrott P, Pratt C, Kleiman N. A randomized double blind placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina (AGENT 2). Presented at Transcatheter Therapeutics, Breaking Trials, Washington, DC, 9/2002. JACC (in review).
Watkins MW, Rubanyi GM. Gene therapy for coronary artery disease: Preclinical and initial clinical results with intracoronary Ad5-FGF4 in Human gene therapy: Current opportunities and future trends edited by Rubanyi GM and Yla-Herttuala S. Springer-Verlag, Heidelberg, Germany, pp 173-188, 2003.
Watkins MW, Kellett MA, Shubrooks SJ, Jr., Hettleman BD, Hearne MJ, Ver Lee PN, Schmitz JM, Ryan TJ, McGrath PD, Piper WE, Dauerman HL, Robb J, Malenka DJ. Percutaneous coronary interventions in bypass grafts in Northern New England 1990 – 2000: Improved acute outcomes in the era of stents. Presented at AHA, Chicago, IL, 11/2002. JACC ( in review).
Niles NW, McGrath PD, Malenka D, Quinton H, Wennberg D, Shubrooks SJ, Tryzelaar JF, Clough R, Hearne MJ, Hernandez F, Jr., Watkins MW, O’Connor GT. Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study. Northern New England Cardiovascular Disease Study Group. JACC 2001;37:1008-15.
Malenka DJ, McGrath PD, Wennberg DE, Ryan TJ, Jr., Kellett MA, Shubrooks SJ, Jr., Bradley WA, Hettlemen BD, Robb JF, Hearne MJ, Silver TM, Watkins MW, O’Meara JR, VerLee PN, O’Rourke DJ. The relationship between operator volume and outcomes following percutaneous coronary interventions in high volume hospitals in 1994 –1996: The northern New England Experience. Northern New England Cardiovascular Disease Study Group [see comments]. JACC 1999; 34:1471–80.
