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Updated: Apr 22, 2026
Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
Angiogenic gene therapy does not cause retinal pathology
Verena Prokosch1, Tobias Stupp, Kristina Spaniol
1University Eye Hospital of Münster, Münster, Germany.
Background:
The potential negative influence of angiogenic gene therapy on the development or progression of retinal pathologies such as diabetic retinopathy (DR) or age-related macular degeneration (AMD) has led to the systematic exclusion of affected patients from trials. We investigated the role of nonviral fibroblast factor 1 (NV1FGF) in two phase II, multinational, double-blind, randomized, placebo-controlled, gene therapy trials (TALISMAN 201 and 211).
Methods:
One hundred and fifty-two subjects with critical limb ischemia or claudication were randomized to receive eight intramuscular injections of 2.5 ml of NV1FGF at 0.2 mg/ml or 0.4 mg/dl or placebo. One hundred and fifty-two patients received a plasmid dose of NV1FGF of up to 32 mg or placebo. All patients underwent a systematic ophthalmologic examination at baseline and at 3, 6 or 12 months following gene therapy. Twenty-six of these patients (Münster subgroup) received a retinal fluorescence angiography at baseline and at final examination.
Results:
Among those 26 patients, four of nine patients with diabetes suffered from nonproliferative DR. Three patients showed non-exsudative AMD. No change of retinal morphology or function was observed in Münster subgroup of both TALISMAN trials independent of the intramuscular NV1FGF dosage applied.
Conclusions:
Angiogenic gene therapy using NV1FGF is safe even in diabetics.
Insights
Nonviral fibroblast growth factor 1 (NV1FGF) gene therapy showed no negative effects on retinal health in patients with critical limb ischemia, including those with diabetes, suggesting safety for diabetic retinopathy patients.
Area of Science:
- Ophthalmology
- Gene Therapy
- Vascular Biology
Background:
- Patients with diabetic retinopathy (DR) and age-related macular degeneration (AMD) are often excluded from angiogenic gene therapy trials due to safety concerns.
- The safety of nonviral fibroblast growth factor 1 (NV1FGF) gene therapy in these patient populations requires investigation.
Purpose of the Study:
- To evaluate the safety and potential ocular effects of NV1FGF gene therapy in patients undergoing trials for critical limb ischemia.
- To assess the impact of NV1FGF on retinal morphology and function in patients with and without diabetes.
Main Methods:
- Two multinational, double-blind, randomized, placebo-controlled phase II trials (TALISMAN 201 and 211) involving 152 subjects with critical limb ischemia.
- Systematic ophthalmologic examinations and retinal fluorescence angiography were performed at baseline and follow-up intervals (3, 6, or 12 months).
- Analysis focused on a subgroup of 26 patients (Münster subgroup) who received retinal imaging.
Main Results:
- Among the 26 patients in the Münster subgroup, four of nine diabetic patients had nonproliferative DR, and three had non-exudative AMD.
- No changes in retinal morphology or function were observed in the Münster subgroup, irrespective of the NV1FGF dosage administered.
Conclusions:
- Intramuscular NV1FGF angiogenic gene therapy is safe for patients with critical limb ischemia, even those with diabetes.
- The findings support the potential safety of NV1FGF in patients with retinal vascular conditions like DR and AMD.
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