Favorable Vision Effects of Retinal Gene Therapy for Choroideremia
By Lynda Seminara
Selected By: Deepak P. Edward, MD
Journal Highlights
Nature Medicine
2018;24:1507-1512
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Choroideremia is a chronic X-linked retinal degeneration that leads to blindness because of deficiency in the Rab escort protein 1 (REP1). Xue et al. designed an adeno-associated viral vector to express REP1 and then evaluated it in a gene therapy trial during which it was injected into patients with choroideremia. Compared with control eyes, and despite complications in two patients, the treated eyes had substantial improvement in visual acuity (VA; 4.5-letter gain vs. 1.5-letter loss). Moreover, the treatment was well tolerated.
The two-year study was conducted at Oxford Eye Hospital and included 14 patients. All participants were male (age range, 25-73 years) and had confirmed null mutations of the CHM gene. Each patient received a single subretinal injection of a virus containing the missing gene. The injection was administered to one eye of each patient; the untreated fellow eye served as the control. The primary endpoint was vision change from baseline to two years in treated versus untreated eyes.
Initially, 12 patients were enrolled. However, complications in two patients (related to vector administration) led to a 24-month delay and a protocol change to improve the surgical technique and immune-suppression regimen. The ethics committee approved an extension of the trial, including recruitment of two additional patients, so that 12 patients would receive the per-protocol therapy and follow-up, as originally planned.
The gain in vision was at least 1 line in six treated eyes and at least 3 lines in three treated eyes. In general, the VA gains and recovery occurred within six months of the treatment. Small gains in VA were noted for eyes with end-stage choroideremia, which otherwise would have declined rapidly. Longer follow-up, up to five years for some patients (mean, 3.6 years), confirmed that the improvements had been maintained.
The findings suggest that a single treatment with a single gene may be sufficient to prevent blindness and, perhaps, ultimately cure other debilitating genetic conditions. (Also see “High-Dose Gene Therapy and BCVA in Choroideremia.”)
The original article can be found here.