Overview
In preclinical studies, our BBS1 novel gene therapy modified the underlying disease of BBS, rescuing vision loss by halting retinal degeneration, stopping BBS-induced weight gain and the development of obesity.1,2
Human Phase 1 trials are anticipated to begin enrollment in the middle of 2025.
AXV-101, a New Codon-Optimised BBS1 AAV9 Vector Halts Photoreceptor and Outer Nuclear Retinal Layer Organisation Degeneration in a Dose-Dependent Manner
Chief Scientific Officer, Dr Victor Hernandez, delivered an insightful presentation on the first gene therapy for the prevention of blindness in Bardet-Biedl Syndrome (BBS) at The Global Cell & Gene Therapy Summit 2024.
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AXV-101, a new codon-optimised BBS1 AAV9 vector, halts photoreceptor and outer nuclear retinal layer degeneration in a dose-dependent manner
Bardet-Biedl syndrome is a debilitating inherited condition characterized by early-onset retinal blindness and severe obesity among other significant clinical problems. We have demonstrated that AXV-101 can halt functional and structural retinal degeneration in the murine mutant (M390R (Bbs1)) retinae in a dose dependent manner. The medium tested dose (3.33x1012vg/ml) is sufficient to sustain photoreceptor survival without any safety concerns.
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Complete rescue of BBS1 neurometabolic syndrome, brain ventriculomegaly and obesity with a unilateral intracerebroventricular delivery of an AAV9 expressing a codon-optimised BBS1 sequence
Intracerebroventricular (ICV) delivery of an Adeno-associated virus 9 (AAV9) expressing human BBS1 (hBBS1) is able to ameliorate the neurometabolic phenotype in the Bbs1M390R/M390R mice.
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Codon-optimisation for Bardet-Biedl Syndrome 1 (BBS1) and Bardet-Biedl Syndrome 10 (BBS10) genes for AAV constructs
Our results show that a precise analysis of different constructs and codon-optimised sequences, is a requisite first step to test new constructs for AAV vectors before assessing for actual pharmacological efficacy.
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Gene therapy results in long-term rescue of photoreceptor function in a mouse model for Bardet-Biedl Syndrome 1
The low levels of expression of BBS1 in photoreceptors may explain the inability to successfully rescue the retinal phenotype. We therefore explored the therapeutic effect of delivering BBS1 to the retinal pigmented epithelium cells, which are highly ciliated and crucial for photoreceptor survival.
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1Goswami R, et al. Front. Oncol. 2019;9:297. 2Fernandes Freitas Martins M, et al. ESCGT; 19–22 Oct 2021, Virtual Congress.