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.