Gene Therapy Treatment for Patients with AMD

gene therapy

Before gene therapy, people have been unsuccessfully battling macular degeneration or age-related macular degeneration (AMD or ARMD), a medical condition that may result in blurred or no vision in the center of the visual field. However, it seems that hope is finally surfacing, thanks to gene editing. In recent research led by Brad Gelfand, Ph.D. whose focus is primarily on the more common, and currently untreatable, dry form macular degeneration, a link between age-related macular degeneration (AMD) in mice and vision loss in people 60 and older were found. This studyChronic Dicer1 Deficiency Promotes Atrophic and Neovascular Outer Retinal Pathologies in Micewas first published January 21, 2020, in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) journal.

Gene therapy: The Cure for AMD?

The team found that the absence of the Dicer enzymewhich is lost with age and leads to an overgrowth of blood vessels in the retina and other damagescould drive both wet and dry forms of AMD. They were able to restore the enzyme in mice by adopting a form of gene therapy already used to treat other eye diseases in people. With further studies, they are hoping that the same approach could be used to treat both forms of AMD safely and effectively, a first for the treatment of dry age-related macular degeneration. It could also significantly improve treatment for wet AMD.

Millions of people are affected by the degeneration of the retinal pigmented epithelium (RPE) and aberrant blood vessel growth in the eye, which are advanced-stage processes in blinding diseases such as AMD. RNase DICER1 is an essential factor in micro-RNA biogenesis and its loss is implicated in RPE atrophy. However, the effect of this loss in choroidal and retinal neovascularization still has to be established.

The Missing Link

Using two independent hypomorphic mouse strains and a separate model of postnatal RPE-specific DICER1 ablation with spontaneous RPE degeneration and choroidal and retinal neovascularization, they found out that DICER1 hypomorphic mice that were lacking in critical inflammasome components or the innate immune adaptor MyD88 developed less severe RPE atrophy and pathological neovascularization. The abundance of DICER1 also reduced spontaneous choroidal neovascularization in retinas of the JR5558 mouse model. Moreover, adeno-associated vector-mediated gene delivery of a truncated DICER1 variant (OptiDicer) was able to reduce spontaneous choroidal neovascularization in JR5558 mice. With these test results, the repertoire of DICER1 in preserving retinal homeostasis by preventing both RPE degeneration and pathological neovascularization is significantly expanded. 

The discovery of the relationship between the wet and dry AMD is a milestone that will eventually lead to the development of a Dicer-based treatment, a feat that will take several more years before patients can fully utilize it. The researchers are continuously working on the treatment that could improve the patients’ vision impaired by AMD

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