Seeing a Brighter Future: A Novel Treatment for Retinitis Pigmentosa

Seeing a Brighter Future: A Novel Treatment for Retinitis Pigmentosa

Vision is something that most people take for granted until it is gone. Without the ability to drive, read, or even walk, 17-year-old Christian Guardino has firsthand experience with severe visual deficits.1 Christian is a high school senior from Long Island who has a disease known as retinitis pigmentosa (RP). RP is a genetic disorder characterized by the death of cells in the retina.2 Christian is one of roughly a million people worldwide who suffer from this disease; it is present in about one in every 4,000 individuals.3

When light enters the eye, the lens focuses it onto the retina, a layer of tissue responsible for the early stages of visual processing. The retina contains rod and cone photoreceptor cells, which transform light into electrical signals for neural processing, also known as phototransduction. Clinically, RP presents with dark pigment deposits as a result of photoreceptor degeneration.2 There are three main stages of the disease. The initial stage is characterized by night blindness, which may be hard to notice at first.3 Night blindness is a sign that the retinal cells are beginning to degenerate. At this stage, RP is very difficult to diagnose, especially if there is no family history of the disease. The initial stage often occurs in adolescents; however, RP can develop any time between early childhood and adulthood.4 The second intermediate stage is where the night blindness becomes more evident, and most diagnoses are made.3 At this point, signs of visual loss during the day also begin to occur, starting at the periphery of the visual field. The final advanced stage is characterized by high numbers of retinal pigment deposits and severe rod degeneration. By the time patients reach this stage most have serious tunnel vision, and cannot move autonomously.3


“Patients like Christian lose their vision at a rate of anywhere between 2-14% per year.”

RP mainly affects the rod photoreceptor cells, which are found around the outer edges of the retina. The disease is caused by mutations in rod cells, which lead to problematic changes in retinal physiology.4 The mutations cause rod degradation and death, and ultimately vision loss. Patients like Christian lose their vision at a rate of anywhere between 2-14% per year.5 In most cases, inherited RP is monogenic.4 Interestingly, the causative mutation varies greatly among individuals; there are over 3,000 known mutations in over 100 different genes that cause RP. There are a variety of ways that these mutations can cause rod cell death.4 Mutations disrupt important cellular functions in rod cells and their supporting tissues, such as protein trafficking, photoreceptor cell differentiation, mRNA splicing, and cytoskeletal function.3


“In December 2017, the FDA approved the first gene therapy treatment for RP, known as Luxturna.”

Treatment of RP is challenging. There are few drugs currently on the market for the disease. However, the retina is a prime candidate for gene therapy treatment. Gene therapy is a technique that alters a patient’s genes to help treat their disease. It is at the forefront of treatment for many genetic disorders, especially those that are challenging to treat with standard drugs. The retina is a good target for gene therapy since it is easily accessible and is compartmentalized from the rest of the body which helps reduce any major side effects of the treatment.5 In December 2017, the FDA approved the first gene therapy treatment for RP, known as Luxturna.1 Luxturna is a drug given surgically by injection to the eye which targets RP caused by a mutation in a gene called RPE65.5,6 When healthy, RPE65 produces an enzyme that is important in cellular processes that help maintain vision. A mutation in RPE65 means that the gene cannot properly produce this enzyme, which leads to vision loss. Additionally, the gene cannot correctly form its cellular proteins, which causes toxic versions of the proteins to accumulate, eventually leading to cell death. To facilitate effective treatment of RP, Luxturna delivers a non-mutated copy of the RPE65 gene to cells in the retina.6 The drug binds to the surface of retinal cells, then enters the cells and delivers the RPE65 gene directly to the nucleus, where it is replicated.

The FDA decided to approve Luxturna based on its success in recent clinical trials. Christian had the chance to participate in one of these trials early last year.1 Patients who received Luxturna had better vision in low light levels and improved visual fields, measured up to one-year post-treatment.7 Although Christian’s vision is not perfect, he is now able to see in lower levels of light. Christian’s mother shares that “[…] he has seen stars for the first time.”1 Luxturna is an exciting new advance in gene therapy for the treatment of RP. Overall, Luxturna provides patients with better vision, thereby drastically improving their quality of life.

Despite these successes, it is also important to consider some of the less positive aspects of the treatment. The drug’s clinical trials show few serious adverse effects. However, it is also important to consider the more mild effects of the drug. Overall, 73% of patients experienced some mild ocular adverse event after receiving treatment.6 The most common events were inflammation, experienced by 22% of patients, and an increase in intraocular pressure, experienced by 20% of patients. In a few cases, these side effects led to glaucoma and vision loss. Also, systemic effects such as nausea, vomiting, and fever each occurred in about one-third of patients.6 Additionally, it is important to remember that Luxturna only treats RP patients who have a mutation in the RPE65 gene. The RPE65 gene mutation accounts for under 1% of total RP cases.3 Gene therapy can only target a specific gene, and for a genetically heterogeneous disease such as RP, this means that not all patients will be able to benefit from this treatment.

Retinitis pigmentosa is a degenerative retinal disease that causes vision loss. It affects one in every 4,000 individuals, including Christian.3 The disease is caused by a variety of different mutations in genes that affect the rod cells and the process of phototransduction in the eye. A new advance in the field of gene therapy, a drug called Luxturna, allows for successful improvement of the condition, but only in a small number of individuals. To help others with this disease and restore some of their vision and quality of life, it is important to continue to explore the field of gene therapy and look for other RP treatments.


Works Cited:

1. McGinley L. FDA approves first gene therapy for an inherited disease. The Washington Post. https://www.washingtonpost.com/news/to-your-health/wp/2017/12/18/fda-approves-first-gene-therapy-for-an-inherited-disease-childhood-blindness/?utm_term=.892ac368086a. Published 2017.

2. Baumgartner WA. Etiology, pathogenesis, and experimental treatment of retinitis pigmentosa. Medical Hypotheses. 2000; 54(5): 814-824. doi: 10.1054/mehy.1999.0957.

3. Hamel C. Retinitis pigmentosa. Orphanet J Rare Dis. 2006; 1: 40. doi: 10.1186/1750-1172-1-40.

4. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. The Lancet. 2006; 368(9549): 1795-1809. doi: 10.1016/S0140-6736(06)69740-7.

5. Dias MF, Joo K, Kemp JA, et al. Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives. Prog Retin Eye Res. October 2017. doi: 10.1016/j.preteyeres.2017.10.004.

6. U.S. Food and Drug Administration. FDA Briefing Document Advisory Committee Meeting: BLA 125610 Voretigene Neparvovec Spark Therapeutics, Inc. U.S. Food and Drug Administration; 2012. Available at: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/CellularTissueandGeneTherapiesAdvisoryCommittee/UCM579290.pdf.

7. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. The Lancet. 2017; 390(10097): 849-860. doi:10.1016/S0140-6736(17)31868-8.


Cite This Article:

Sharpe I., Chan G., Zhang B., Palczewski K., Lewis K., Ho J. Seeing a Brighter Future: A Novel Treatment for Retinitis Pigmentosa. Illustrated by C. Nguyen. Rare Disease Review. August 2018. DOI:10.13140/RG.2.2.28985.83049.

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