AAVantgarde Bio has commenced its first-in-human Phase 1/2 LUCE-1 clinical trial (NCT06591793) with the initial dosing of a patient. The trial is evaluating AAVB-081, also known as AAV8.MYO7A, an adeno-associated virus (AAV) vector-based gene therapy, for the treatment of retinitis pigmentosa associated with Usher syndrome type 1B (USH1B).
AAVB-081: A Novel Gene Therapy Approach
AAVB-081 is a dual hybrid product composed of two AAV8 vectors designed to deliver a functional copy of the Myo7A gene. Each vector carries half of the transgene, which recombines within the cell due to its large size exceeding the capacity of a single AAV vector. The therapy is administered subretinally.
LUCE-1 Trial Details
The multicenter, open-label LUCE-1 trial is structured as a dose-escalation study. Participants will receive one of three planned dose levels. The trial aims to enroll a total of 15 patients with USH1B, aged 18 to 50 years. The primary endpoint focuses on the number and severity of treatment-related adverse events. Secondary endpoints include changes from baseline in microperimetry and static perimetry, assessed over a 61-month period. The study is currently recruiting at the University of Campania Luigi Vanvitelli in Naples, Italy.
Expert Commentary
Francesca Simonelli, Head of the Ophthalmology Unit at the University Hospital of Campania Luigi Vanvitelli, stated, "I am delighted to be involved as principal investigator in this first-in-human phase 1/2 clinical study of AAV-081 for patients with retinitis pigmentosa related to USH1B. Through this innovative program, we aim to revolutionize our approach to understanding and treating these underserved patients. We are poised to generate robust evidence that will not only advance scientific knowledge but also directly impact patient care."
Broader Context of Usher Syndrome Research
AAV-081 is part of a growing field of advanced therapeutics targeting various forms of Usher syndrome. Research findings related to USH1B, Usher syndrome Type 1F, Usher syndrome type 2C, and other forms have been reported in recent years, according to the Usher Syndrome Coalition.
Alternative Approaches: Gene Editing for Usher Syndrome Type 2A
Zheng-Yi Chen, DPhil, and colleagues at Mass Eye and Ear and Harvard Medical School are exploring gene-editing approaches for Usher syndrome type 2A (Ush2A). Their work focuses on exon skipping to target frequent Ush2A mutations, aiming to restore Ush2A protein production and function. "Our work focuses on the development of gene editing to treat hearing loss and vision loss in Ush2A, the most common form of Usher syndrome," Chen told CGTLive. He added that conventional AAV vector-based gene therapy is not suitable for the large Ush2A gene, necessitating a gene-editing strategy.
