Target Late AMD
The gene therapy approach based on Target AMD 1.0, consists in the transplantation of a patient’s own iris pigment epithelial (IPE) cells genetically modified to overexpress therapeutic genes aiming at recovering a healthy retinal environment, stopping vessel growth (in wet AMD), or reducing inflammation and oxidative stress (in dry AMD). In this approach, only around 10,000 IPE cells can be harvested from the patient and act as a long-term acting drug-delivery system but cannot replace larger numbers of lost cells.
Stem cells are immature cells with the capacity to mature into cells required by our body due to regular renewal or after injury. Our bone marrow, e.g., contains stem cells for the renewal of blood cells. In stem cell therapy, this capability is used to induce the maturation into special cell types lost in distinct diseases. A particular type of stem cells, the induced pluripotent stem cells (iPSC), are of special interest, as they can be produced from every patient in large quantities with the option to mature into any cell of our body. Thus, applying the approach, cells lost in advanced AMD could be replaced.
In the present approach, it is planned to collect renal cells in patients’ urine for the production of patient-derived (autologous) iPSC. Next, these iPSC will be matured into retinal pigment epithelial (RPE) cells and multiplied to be transplanted to the patients’ retina. However, we hypothesize that cells transplanted into a diseased retina, which represents a “toxic” environment, will be damaged over time and get lost, too. We therefore propose to combine the stem cell approach with our gene therapy. RPE cells, derived from iPSC, will be genetically modified to overexpress therapeutic genes to help themselves to survive by recovering a healthy environment.
In the current project we establish the protocol for the maturation of RPE cells from iPSC.
Definition: Oxidative stress is a term for biochemical reactions induced by the processing of oxygen. These processes occur permanently in our body and particularly in the retina. In a healthy environment, harmful byproducts of the reactions are eliminated. In age and disease, however, this so-called antioxidant defense is weakened, harmful byproducts accumulate and damage cells.
Induced pluripotent stem cells are biotechnologically created stem cells derived from mature skin, blood, hair or other cells. A small biopsy is taken, and the cells are set back to a immature, stem cell status (induced). Then, applying distinct culture protocols, the cells can mature into any cell of our body (pluripotent). After multiplying the number of the newly matured cells, they can be transplanted to replace cells lost due to trauma or disease.