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

TargetAMD Therapeutic Approach Surgery

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

TargetAMD Therapeutic Approach Surgery

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.

Sur­gic­al ap­proach

TargetAMD Therapeutic Approach Surgery