AAV gene therapy encoding equine IL10

Equine recurrent uveitis (ERU) is a spontaneous, painful, and vision
threatening disease affecting up to 25% of equine populations worldwide.
Current treatments of ERU are non-specific and have many side effects
which limits them to short-term use.  In order to
develop an effective therapy for ERU, we investigated the use of
adeno-associated virus (AAV) gene therapy, exploiting a natural immune
tolerance mechanism induced by equine interleukin-10
(Equine-IL10). The purpose of this study was to evaluate the
therapeutic efficacy of a single intravitreal (IVT) dose of
AAV8-Equine-IL10 gene therapy for inhibition of experimental autoimmune
uveitis (EAU) in rats. Each rat was dosed intravitreally
(IVT) in both eyes with either balanced salt solution (BSS) (control;
n=4), AAV8-Equine-IL10 at a low dose
(2.4x109 vg; n=5) or high dose (2.4x1010 vg; n=5). EAU
was induced in all groups of rats 7 days after IVT injections and
euthanized 21 days post-injection.  Ophthalmic
examination and aqueous humor (AH) cell counts were recorded with the
observer blinded to the treatment groups. Histopathology and qPCR were
performed on selected ocular tissues. Data presented herein demonstrate
that AAV8-Equine-IL10 treated rats exhibited a significant decrease in
clinical inflammatory scores and AH cell counts compared to BSS-treated
EAU eyes on days 10, 12 and 14 post EAU induction at both administered
vector doses.  Mean cellular histologic infiltrative
scores were also significantly less in AAV8-Equine-IL10 dosed rats
compared to the BSS group. Intravitreal injection of AAV8-Equine-IL10
resulted in Equine-IL10 cDNA expression in the ciliary body, retina,
cornea, and optic nerve in a dose-dependent manner.  A
single IVT injection of AAV8-Equine-IL10 appeared to be well-tolerated and
inhibited EAU even at the lowest administered dose. These results
demonstrate safety and efficacy of AAV8-Equine-IL10 to prevent EAU and
support continued exploration of AAV gene therapy for the treatment of
equine and perhaps human recurrent uveitis.