Miquel Vila-Perello, PhD, co-founder and CEO of SpliceBio, discusses an investigational dual adeno-associated virus (AAV) gene therapy in development for patients with Stargardt disease.
Stargardt disease is a genetic eye disorder characterized by progressive vision loss caused by abnormal accumulation of lipofuscin in the cells within the macula. Patients with Stargardt disease also have problems with night vision and color vision. It is most commonly caused by genetic changes in the ABCA4 gene but, in rare cases, may be caused by genetic changes in other genes. There are currently no approved treatments for this disease.
Difficulties in developing therapies, especially for those that address the underlying cause of Stargardt disease, are due to the size of the ABCA4 gene. As Dr. Vila-Perello explains, AAVs have limited cargo capacity and the ABCA4 gene is larger than what can fit. This causes challenges in delivering a healthy copy of the gene to patients and effectively treating their underlying disease.
SB-007 is an investigational dual AAV gene therapy designed to restore expression of a functional, full-length ABCA4 protein in the retina. A novel protein splicing platform uses two AAV serotype 8 (AAV8) vectors to overcome the size limitations of conventional AAVs, reconstituting biologically active ABCA4 through protein trans-splicing in target photoreceptor cells. SpliceBio has received Orphan Drug designation for SB-007 from the US Food and Drug Administration (FDA) and the European Commission.
In preclinical models, SB-007 demonstrated robust pharmacological activity, durable retinal expression, and a favorable safety profile.
SpliceBio is currently enrolling participants in ASTRA, a phase 1/2 multicenter, global clinical trial designed to evaluate the safety, tolerability and efficacy of SB-007. The company expects to enroll approximately 57 patients aged 12 to 65 with Stargardt disease into Part B. Part A of the study evaluated three dose levels of subretinal SB- 007 in an open-label, dose-escalation design. Part B is randomized, controlled and masked, and will evaluate two dose levels of subretinal SB-007 compared to an untreated control group, with a follow-up of 96 weeks. The primary endpoint is safety and tolerability, assessed by the incidence and severity of ocular and nonocular adverse events. For more information on the trial, visit ClinicalTrials.gov (NCT06942572).
To learn more about Stargardt disease and other rare eye conditions, visit https://checkrare.com/diseases/ophthalmology-eye-diseases/
