Researchers have announced recruitment of the first patient in a clinical trial of a an experimental AAV gene therapy for the treatment of X-linked retinitis pigmentosa (XLRP). The interventional clinical study (termed FT-002) is sponsored by a recent USA and China group (Frontera), based in Bedford, Massachusetts and Shanghia, China. The clinical study will be supported by a number of clinical ophthalmic experts including Prof. Jean Bennett at the Perelman School of Medicine, University of Pennsylvania, Professor Fraser Wright at the Center for Definitive and Curative Medicine at Stanford University and Prof Mark Kay, at the Department of Genetics, at Stanford University School of Medicine.
X-linked retinitis pigmentosa (XLRP) is an incurable genetic disease that causes blindness in males affecting approximately one in 15,000 people. The disease is caused by a defect in the RPGR gene (GTPase regulator gene) which is located on the X-chromosome. Together with mutations in RP2, these two genes account for a significant majority of cases of XLRP. Over 300 mutations occur in the RPGR gene, most of which in the open reading frame exon (ORF15), causing an abnormally short protein that is expressed in the connecting cilium of photoreceptors, and is an important component of all ciliated cells in the body. Mutations in the RPGR gene can be associated with a rod-cone or cone-rod dystrophy phenotype. The most common presentation is as a rod-cone dystrophy. It is one of the most severe forms of RP with nyctalopia in most affected males before 10 years of age and progression to legal blindness by the third to fourth decade. The disorder is initially identified with difficulties in scotopic visual function, where there is a predominant loss of rod photoreceptors. Simultaneously, peripheral vision deteriorates, resulting in visual field constriction on perimetry findings. The majority of cases present with a rod-cone dystrophy-type disease progression, where central visual acuity is initially less impaired than the peripheral field loss. The fovea is ultimately affected in all cases during the late stages of the disease by subsequent cone photoreceptor degeneration.
The experimental AAV-RPGR treatment was administered to the first patient in China, and that the XLRP population, due to RPGR gene variants, are estimated to have 3.4-4.4 per 100,000 in Europe / USA (approximately 20,000 patients) and approximately 30,000 to 50,000 XLRP patients in China. According to the sponsor (Frontera), Dr. Yong Dai, Ph.D., commented that the recruitment has now accelerated the clinical work and that “we believe FT-002 could greatly improve the quality of life for XLRP patients for whom there are currently no effective treatments. This year, the company expects to advance additional product candidates into preclinical and clinical studies, which we believe may provide more patients with curative opportunities.”