June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
SPVN06, a novel mutation-independent AAV-based gene therapy, dramatically reduces vision loss in the rd10 mouse model of rod-cone dystrophy
Author Affiliations & Notes
  • Florence Lorget
    SparingVision, France
  • Melanie Marie
    SparingVision, France
  • Hanen Khabou
    SparingVision, France
  • Cardillia Simon
    SparingVision, France
  • Didier Nuno
    EyeCRO, Oklahoma, United States
  • Phillip Vanlandingham
    EyeCRO, Oklahoma, United States
  • Alain Quiambao
    EyeCRO, Oklahoma, United States
  • Rafal Farjo
    EyeCRO, Oklahoma, United States
  • Deniz Dalkara
    INSERM, Paris, Île-de-France, France
    SparingVision, France
  • Jose Alain Sahel
    UPMC, Pittsburgh, Pennsylvania, United States
    SparingVision, France
  • Thierry D Leveillard
    INSERM, Paris, Île-de-France, France
    SparingVision, France
  • Footnotes
    Commercial Relationships   Florence Lorget sparingvision, Code E (Employment); Melanie Marie SparingVision, Code E (Employment); Hanen Khabou SparingVision, Code E (Employment); Cardillia Simon None; Didier Nuno EyeCRO, Code C (Consultant/Contractor); Phillip Vanlandingham EyeCRO, Code C (Consultant/Contractor); Alain Quiambao EyeCRO, Code C (Consultant/Contractor); Rafal Farjo EyeCRO, Code C (Consultant/Contractor); Deniz Dalkara SparingVision, Code C (Consultant/Contractor), SparingVision, Code F (Financial Support); Jose Sahel SparingVision, Code O (Owner), SparingVision, Code P (Patent), SparingVision, Code S (non-remunerative); Thierry Leveillard SparingVision, Code C (Consultant/Contractor), SparingVision, Code F (Financial Support), SparingVision, Code I (Personal Financial Interest), SparingVision, Code O (Owner), SparingVision, Code P (Patent)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 56 – A0029. doi:
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      Florence Lorget, Melanie Marie, Hanen Khabou, Cardillia Simon, Didier Nuno, Phillip Vanlandingham, Alain Quiambao, Rafal Farjo, Deniz Dalkara, Jose Alain Sahel, Thierry D Leveillard; SPVN06, a novel mutation-independent AAV-based gene therapy, dramatically reduces vision loss in the rd10 mouse model of rod-cone dystrophy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):56 – A0029.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : SPVN06 is a proposed gene therapy for patients experiencing vision loss due to rod-cone dystrophy (RCD), regardless of the causative mutation. In all RCD, photoreceptor degeneration is first observed in rods, and subsequently in cones, in large part due to a lack of trophic support. SPVN06 encodes, in a single AAV, the cDNAs for trophic factor Rod-derived Cone Viability Factor (RdCVF) and thioredoxin enzyme RdCVF-Long (RdCVFL), both isoforms of the NXNL1 gene. RdCVF, secreted by rods, protects cones from degeneration by stimulating aerobic glycolysis. RdCVFL is a potent antioxidant protecting cones from oxidative stress. SPVN06 early nonclinical development included several pharmacology studies in rd10 mice, a fast-progressing model of RCD.

Methods : rd10 mice were born and raised in darkness until transferred to regular cyclic light on postnatal day (P) 31 up to study termination at P48. At P15 or P18, the animals received a bilateral subretinal administration of 1 µL of vehicle or SVPN06 at 1E8 vg/eye. Effect of SPVN06 on retinal function and structure were evaluated by optokinetic (OKT), ffERG, optical coherence tomography (OCT) and histology.

Results : A highly significant protection of the visual function (OKT) was noted at P32 (p<0.0001) when the animals received SPVN06 1E8 vg/eye at P18. The level of visual function in SPVN06-treated eyes was similar to wild-type (WT) level versus only ~50% of WT in vehicle-injected eyes. At the later timepoints (P38 and P45), the difference between the 2 groups remained significant, although visual loss continued in both vehicle and SPVN06 treated eyes. H&E staining of the retina at P48 didn’t reveal a protection of the ONL, whereas PNA staining at the same timepoint revealed greater density of the cone outer segments and/or their membrane remnants in SPVN06-treated eyes. When injection was conducted at PN15, no protection of the visual function was noted suggesting an optimal timing (P18) for treatment in this model. There were no significant SPVN06-related changes in ffERG or OCT parameters.

Conclusions : SPVN06 dramatically protects retinal degeneration in rd10 mice, a fast-progressing model of RCD, supporting clinical development.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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