Safety and biodistribution of an equine infectious anemia virus-based gene therapy, RetinoStat(®), for age-related macular degeneration.

The study examines the safety and biodistribution of RetinoStat®, a gene therapy treatment for age-related macular degeneration (AMD) that uses a lentiviral vector derived from equine infectious anemia virus and expresses two proteins to combat disease progression. After being tested in rabbits and macaques, the treatment was found to be well tolerated, localized to the eye, and capable of providing persistent protein expression.

Methodology of Research

• RetinoStat® was tested on two species, Dutch belted rabbits and rhesus macaques, over a period of six months to determine its safety and biodistribution.
• The therapy was administered via a subretinal injection, common in the treatment for wet AMD.
• The levels of human endostatin and angiostatin proteins expressed by RetinoStat® in the vitreous of treated rabbit eyes were monitored, peaking at around a month after dosing and maintained for the duration of the study.
• The animals underwent regular ocular examinations throughout the course of the study.

Results of the Study

• A mild to moderate transient ocular inflammation was observed post-treatment in both species, resolving within a month of dosing.
• No significant long-term changes were observed in the electroretinograms or intraocular pressure measurements post-treatment in either species compared with the baseline readings in the RetinoStat®-treated eyes.
• While no structural changes were found in the eyes, mononuclear cells infiltrated the vitreous, retina, and choroid.
• No antibodies to any of the RetinoStat® vector components or the transgenes could be detected in blood samples from either species.
• The biodistribution analysis showed that the RetinoStat® vector stayed within the ocular compartment.

Conclusions of the Research

• The data suggests that RetinoStat® is well tolerated in the test species, causing only temporary inflammation.
• The therapy was limited to the injected eye area, indicating effective localization.
• RetinoStat® was able to provide persistent protein expression, suggesting its long-term potential in the treatment of AMD.