Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye.
Current therapeutic antiangiogenic biologics used for the treatment of pathological ocular angiogenesis could have serious side effects due to their interference with normal blood vessel physiology. Here, we report the generation of novel antivascular endothelial growth factor-A (VEGF) biologics, termed VEGF "Sticky-traps," with unique properties that allow for local inhibition of angiogenesis without detectable systemic side effects. Using genetic and pharmacological approaches, we demonstrated that Sticky-traps could locally inhibit angiogenesis to at least the same extent as the original VEGF-trap that also gains whole-body access. Sticky-traps did not cause systemic effects, as shown by uncompromised wound healing and normal tracheal vessel density. Moreover, if injected intravitreally, recombinant Sticky-trap remained localized to various regions of the eye, such as the inner-limiting membrane and ciliary body, for prolonged time periods, without gaining access either to the photoreceptors/choriocapillaris area or the circulation. These unique pharmacological characteristics of Sticky-trap could allow for safe treatment of pathological angiogenesis in patients with diabetic retinopathy and retinopathy of pre-maturity.
Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital, Toronto, ON, Canada.
Iacovos P
IP
Michael
Peter D
PD
Westenskow
Sabiha
S
Hacibekiroglu
Alissa Cohen
AC
Greenwald
Brian G
BG
Ballios
Toshihide
T
Kurihara
Zhijie
Z
Li
Carmen M
CM
Warren
Puzheng
P
Zhang
Edith
E
Aguilar
Laura
L
Donaldson
Valentina
V
Marchetti
Takeshi
T
Baba
Samer M
SM
Hussein
Hoon-Ki
HK
Sung
M Luisa
ML
Iruela-Arispe
James M
JM
Rini
Derek
D
van der Kooy
Martin
M
Friedlander
Andras
A
Nagy
D001688:Biological Products / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics; D005123:Eye / Q000187:drug effects*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D001688:Biological Products; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor