Results of the first gene therapy trial conducted at Oregon Health & Science University (OHSU) hold promise for treating one form of age-related macular degeneration (AMD).
The multicenter, Phase I clinical trial revealed that injecting a gene directly into the eye to inhibit blood vessel growth was safe and well tolerated, and it may be able to halt the progression of "wet" macular degeneration. The results were published in the February 2006 issue of Human Gene Therapy.
Wet AMD occurs when an abnormal growth of blood vessels behind the retina bleed and leak fluid, forming scar tissue that damages central vision. An estimated 1.2 million Americans suffer from this form of the disease, and that number is expected to grow as the population ages. Wet AMD, the less common though more severe form of the disease, results in more rapid vision loss than the "dry" form and is responsible for blindness in a disproportionate number of cases.
Researchers took the pigment epithelium-derived factor (PEDF) gene, cloned it into an E1, partial-E3 and E4 deleted adenovirus, and injected it directly into the eye through an intravitreal route. The vector overexpresses PEDF, driven by a CMV promoter, which inhibits formation of abnormal blood vessels through antagonism with VEGF.
Nationwide, 28 people in advanced stages of AMD enrolled in the study. Patients received either a single low-dose or a single high-dose of the adenovirus with the PEDF gene. After following the subjects for a year, researchers found that, on average, those who received a high dose had no growth in their macular lesions at 6 and 12 months post-therapy, while those that received a low dose saw some increase in their lesion size. A larger Phase II clinical trial to further evaluate efficacy is planned. Concerns regarding the inflammatory induction, common to adenoviral administration, appear to be unfounded; no severe adverse events were noted and only 25% of patients developed transient ocular inflammation which was easily controlled. Antibodies versus the virus were not produced by the majority of subjects.
This therapy promises to be broadly applicable for all neovascular diseases of the eye, including retinoblastomas and ocular diabetic complications
Message posted by: Simon Chandler