Treating Stargardt’s disease

Inquiry question: How could ocular gene therapy potentially cure macular degeneration such as  Stargardt’s disease?

Evidence #1: Why is ocular gene therapy not accessible for people with Stargardt’s disease?

Stargardt’s disease is an inherited disease that targets the eye and leads to macular degeneration, the loss of central vision (Boyd, 2019). Macular degeneration happens when the macula, the region of your retina that gives you vision, breaks down (Dunaief, 2019). Furthermore, Stargardt’s disease also causes photoreceptors to deteriorate, photoreceptors convert light into signals that can be recognized by the brain (Dunaief, 2019). The most common cause of Stargardt’s disease is a genetic mutation in a gene called ABCA4, this gene is responsible for creating proteins that clear the photoreceptors from any side effects of vitamin A (Dunaief, 2019).

Ocular gene therapy for Stargardt’s disease would involve replacing the unhealthy ABCA4 gene with a healthy ABCA4 gene (Ziccardi, 2019). For some ocular diseases, this process of replacement can be done, the gene of interest can safely enter the retinal cells because it has been put inside a safe virus, known as adeno-associated virus (AVV) (Dunaief, 2019). However, the ABCA4 gene that is the cause of Stargardt’s disease is too large to be carried into the retina by this virus, therefore, the development of new procedures, such as dual-vectors, is important (Boyd, 2019).

Evidence #2: How does the process of dual-vector delivery work?

Adeno-associated viruses (AAV) vectors have shown low-immunogenicity among clinical trials, thus making it the ideal vector for gene therapy. However, since AAV vectors do not have the capacity for the ABCA4 gene, researchers have discovered that gene therapy for Stargardt’s disease lies in dual-vector AAV technology (Trapani, 2014). Vectors are organisms that spread infection by transporting pathogens from host to host, however, in gene therapy, vectors are modified to spread the benefits of the gene that is being transported (Trapani, 2014). Moreover, this new technology is said to deliver the ABCA4 gene into the retina in two halves; the halves will then reunite to create a fully functioning ABCA4 gene, while still using the desired AAV vectors (McClements, 2017).

Claim: Stargardt’s disease is a form of macular degeneration that targets photoreceptors with a mutation in the ABCA4 gene. Unfortunately, the ABCA4 gene is too large for the traditional AAV to carry into the retina, however, there is always new technology being developed. The most promising of those are dual-vector AAV technology, this is a delivery system where the ABCA4 gene is transported into the retina in halves and then reconnects inside the retina. This way, the preferred use of AAV can be used to treat patients with macular degeneration with larger genes like Stargardt’s disease.

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