Tar­get Dry AMD

Only one the­ra­py ex­ists for the dry form of AMD, which – how­ever — con­cerns about 90% of pa­tients suf­fer­ing from AMD in total. This drug, Sy­fo­vre®, is cur­rently avail­able only in the United States and shows a sim­il­ar ad­min­is­tra­tion route and fre­quency as drugs for wet AMD, and thus, shows com­par­able draw­backs. Dry AMD is caused by in­flam­mat­ory re­ac­tions and oxi­dative stress that re­sults in the ac­cu­mu­la­tion of waste products secreted by the Reti­nal Pig­ment ep­ithe­lial (RPE) cells. These so called drusen fur­ther dam­age the RPE cells un­til they un­der­go cell death. The weakened and lost Reti­nal Pig­ment ep­ithe­lial cell lay­er has two main con­sequences: 1) Im­port­ant neuro­pro­tect­ive factors are in­suf­fi­ciently pro­duced and 2) photorecep­tors lose con­tact with Reti­nal Pig­ment ep­ithe­lial cells. Both lead to dam­age up to the death of photorecep­tors and thus, in the ad­vanced stage, large de­teri­or­ated, cell-less (at­roph­ic) areas of the reti­na.

Based on the Tar­get­AMD 1.0 ap­proach, we aim to trans­plant sub­ret­in­ally auto­log­ous Iris Pig­ment Ep­ithe­lial cells ge­net­ic­ally mod­i­fied with a com­bin­a­tion of two thera­peut­ic genes, one cod­ing for a cell protec­tive factor (Pig­ment Ep­ithe­li­um-De­rived Factor) and one against in­flam­ma­tion and oxi­dative stress (Granulo­cyte Mac­ro­phage Colony-Stim­u­lat­ing Factor). The con­tinu­ous de­liv­ery of these pro­teins to the reti­na shall pre­vent fur­ther loss and de­gen­er­a­tion of the reti­nal Pig­ment ep­ithe­lial and the reti­nal cells.

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.