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  • Favorable Vision Effects of Retinal Gene Therapy for Choroideremia

    By Lynda Seminara
    Selected By: Deepak P. Edward, MD
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    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.