Efficacy and Safety of Gene Therapy Using Adeno-Associated Virus Vector in Patients with Choroideremia
Choroideremia (CHM) is a rare genetically conditioned retinal disease caused by mutations in the CHM gene, leading to a lack of production of the protein REP1 (ras-associated binding escort protein 1). Currently, there is no approved treatment for CHM. The aim of the study (Tübingen Choroideremia Gene Therapy) published last year in the journal JAMA Ophthalmology was to evaluate the safety and efficacy of subretinally applied gene therapy using an adeno-associated virus vector (AAV2), designed to deliver a functional copy of the CHM gene to patients with choroideremia.
Methodology and Course of the Study
An open-label, single-center, randomized phase II clinical trial was conducted from January 2016 to February 2018 and provided treatment results for 6 male patients with a molecularly confirmed diagnosis of CHM over a 24-month period. These patients received one subretinal injection of 0.1 ml containing 1011 particles of AAV2-REP1 in one randomly selected eye during vitrectomy.
The primary endpoint was the change in best-corrected visual acuity (BCVA) on ETDRS optotypes in the treated eye compared to the control eye at baseline and after 24 months.
Results
The average age of the 6 participants at the start of the study was 54.9 years (standard deviation [SD] 4.1). The average BCVA of the study eyes was 60.3 (SD 13.4), corresponding to a Snellen equivalent of approximately 20/63; for the control eyes, it was 69.3 (SD 20.6), corresponding to a Snellen equivalent of approximately 20/40. The change in BCVA after 24 months was 3.7 (7.5) in treated eyes and 0.0 (5.1) in control eyes (p = 0.43).
A total of 28 adverse events were reported, all associated with the surgical procedure (e.g., conjunctival hyperemia, foreign body sensation) and none were considered serious.
Conclusion
Although no statistically significant difference was found, gene therapy with AAV2-REP1 led to the maintenance or improvement of visual acuity in 6 participants. Further research will be needed to more precisely define the efficacy and safety of gene therapy in CHM.
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Source: Fischer M. D., Ochakovski G. A., Beier B. et al. Efficacy and safety of retinal gene therapy using adeno-associated virus vector for patients with choroideremia: a randomized clinical trial. JAMA Ophthalmol 2019 Aug 29, doi: 10.1001/jamaophthalmol.2019.3278 [Epub ahead of print].
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