Healthcare Professionals

Therapeutical approach and surgery

Therapeutic approaches

The goal of our therapeutic approaches is to provide patients with treatment that is:

Safe
Efficient
Long-lasting (only one life-long intervention)
Quick and simple to administer
Cheap

The initial approach, developed by the TargetAMD consortium, comprised the harvest of an iris biopsy, immediate, non-viral genetic modification of the cells by integration of one gene of interest and subretinal transplantation of the autologous cell product. Since then, the approach has been broadened to treat both forms of AMD, early and late stages of the disease using more than one therapeutic gene and stem cell-technology.

Treatment of early neovascular AMD (nAMD)

Reduction of the imbalance between the vascular endothelial growth factor (VEGF) and the pigment epithelium-derived factor (PEDF): Around 10’000 autologous iris pigment epithelial (IPE) cells are transfected ex vivo by electroporation (Cliniporator, IGEA, Italy) introducing the Sleeping Beauty transposase 100X and the transposon plasmid encoding the gene for PEDF into the host cells’ genome.

The stably, randomly integrated gene of interest is transcribed, translated and the PEDF protein overexpressed inhibiting VEGF-mediated neovascularization. The Good Manufacturing Practice (GMP)-grade manufacture of the Advanced Medicinal Therapy Product tIPE has been validated, and the application for a phase Ib/IIa clinical trial has been submitted to the cantonal ethics commission, CCER, and to the Swiss regulatory authority, Swissmedic. The CCER already approved the trial; Swissmedic requested additional evidence of the treatment’s stability and safety.

TargetAMD 1.0 approach

Treatment of early avascular AMD (aAMD)
Reduction of inflammation and oxidative stress:

As in the first approach, around 10,000 autologous IPE cells will be harvested and genetically modified using the Sleeping Beauty transposon system. PEDF also functions neuroprotective and will support recovery of a healthy retinal environment. Additionally, the antioxidative neuroprotective growth factor GM-CSF (granulocyte macrophage-colony forming factor) will be delivered by a second transposon plasmid to reduce oxidative stress and inflammation. Thus, further loss of RPE (retinal pigment epithelial) cells will be prevented, a neuroprotective retinal environment re-established, and the progression of the retinal degeneration inhibited. This approach is in pre-clinical testing.

Treatment of late stage AMD (AMD)

Replacement of degenerated RPE cells by iPS-derived, genetically enhanced RPE cells: Autologous iPS (induced pluripotent stem) cells will be generated from urine renal tubular cells, differentiated to RPE cells, proliferated, and genetically modified to overexpress the gene coding for PEDF. A suspension containing a large number of RPE cells will be then transplanted in the diseased retina to replace degenerated RPE cells and to recover a healthy retinal environment. This approach is in development.

The late stage AMD approach

Surgical approach

The surgical protocol developed for the treatment of patients suffering from AMD will comprise the harvest of autologous IPE cells in the operating room under general anesthesia. The iridectomy will be transported to the clean room, where IPE cells will be isolated and transfected in a GMP-grade in-house production using the SB100X transposon system. Next, the transfected IPE cells will be transported back to the operating room, where they will be implanted subretinally to the same patient within the same surgical session, completing the approximately 60 minutes lasting surgical procedure.

Thera­peut­ic­al ap­proach and sur­gery

Tar­get­AMD 1.0 ap­proach

The late stage AMD ap­proach

Sur­gic­al ap­proach

Therapeutical approach and surgery

TargetAMD 1.0 approach

The late stage AMD approach

Surgical approach