The Clinical Research Institute (CRI) of the Foundation Fighting Blindness (FFB) has announced the enrollment of the first patient in a 4-year study to delineate the natural history of patients with mutations in the USH2A gene (USH2A). Mutations in USH2A are understood to be the leading cause of Usher syndrome type 2A and vision loss from autosomal recessive retinitis pigmentosa. The study aims to recruit eligible participants from 21 sites worldwide, including European centres in Belgium, France, Germany, the Netherlands and the UK.
Entitled “The Rate of Progression in USH2A-related Retinal Degenerations”, or the “RUSH2A” study, the trial aims to recruit up to 120 patients with the ultimate aim of accelerating the development of outcome measures for clinical trials and to build a deeper understanding of USH2A-related retinal degenerations and pathology. Usher syndrome type 2A is inherited as an autosomal recessive disorder characterized by hearing loss from birth, together with progressive vision loss beginning in teenage years or early adulthood. Vision loss is due to RP, while hearing loss varies within and among families. According to the trial details registered at clinical trials.gov, the primary objectives of the natural history study are to:
-characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene over 4 years, as measured using functional outcome measures, full-field stimulus threshold, ERG and visual acuity;
-characterize the natural history of retinal degeneration associated with biallelic pathogenic mutations in the USH2A gene over 4 years, as measured using structural outcome measures;
-investigate structure-function relationships for insights into the mechanisms of retinal degeneration by relating changes in SD-OCT EZ area to visual field progression in individuals with biallelic pathogenic mutations in the USH2A gene;
-assess for possible genotype, phenotype and environmental risk factors with progression of the outcome measurs at 4 years individuals with biallelic pathogenic mutations in the USH2A gene.
Commenting on the initiation milesone, the study chair, Dr. Jacque Duncan, stated, “A major challenge in providing prognoses for patients with USH2A mutations, and in designing clinical trials for potential therapies, is the wide variability in symptoms, rates of progression and severity of the disease. This study will help the field gain a better understanding of how USH2A mutations cause vision and hearing loss in some patients and why other patients with normal hearing at birth develop vision loss.”