Overlaying Retinitis Pigmentosa (RP) Management in the MENA Region

An analysis of the current scenario and future perspective of Retinitis Pigmentosa epidemiology and management specific to the MENA region!

Retinitis Pigmentosa is inherited retinal dystrophy caused by the gradual atrophy of the photoreceptor cells in the retina and characterized by progressive degeneration of the retina and progressive vision loss in affected individuals. Retinitis Pigmentosa is classified based on clinical impact as nonsyndromic or simple (not affecting other organs or tissues), syndromic (affecting other neurosensory systems such as hearing), and systemic (affecting multiple tissues). Among all subtypes, nonsyndromic Retinitis Pigmentosa is highly prevalent in all geographic regions (more than 50% of Retinitis Pigmentosa cases are occupied by nonsyndromic Retinitis Pigmentosa). As per the National Organization of Rare Diseases (NORD), this inherited vision disorder affects nearly 1 in 3,000–1 in 4,000 people worldwide. In regions like United Arab Emirates (UAE), Saudi Arabia, Kuwait, and others, the disease is more prominent affecting nearly about two and half times of other countries like the US and Europe mainly due to consanguineous marriages that are more common in the population residing in the MENA region and thus highly prevalent founder mutations.

Although epidemiological studies are minimal for Retinitis Pigmentosa in all geographic regions, some studies have concluded that the prevalence of Retinitis Pigmentosa is higher in countries residing in the MENA region. For instance, one study from Israel’s Jerusalem region showed the prevalence of Retinitis Pigmentosa is 1 in 2,086, and the prevalence of Retinitis Pigmentosa was higher among Arab Muslims (1 in 1,798) ^a. Other countries from the MENA region also showed a similar trend; for example, in Kuwait, Retinitis Pigmentosa has been the leading cause of blindness driven by a high prevalence of consanguineous marriages ^b,c. The same study stated that the rate of Retinitis Pigmentosa was three times as high as in the younger subgroup, followed by optic atrophy, congenital malformations, and albinism.

Autosomal recessive retinal diseases are likely to be a common thing in the region where consanguineous and intracommunity marriages are still the norm. Even with the rising prevalent cases in this region, the management has remained a challenge. To date, the diagnosis, prognosis, and management of Retinitis Pigmentosa continue to be challenging, related mainly to an incomplete understanding of the pathophysiology of the disease process, complexity due to the involvement of several genes, and a lack of evidence-based standardized curative therapies for all forms of Retinitis Pigmentosa in major geographies.

The majority of the current Retinitis Pigmentosa treatment market for all forms of Retinitis Pigmentosa is revolving around off-label therapies like nutritional supplements (e.g., Vitamin A Palmitate, Docosahexaenoic acid (DHA), and vitamin E) and supportive measures (e.g., optical aids, sun lenses, magnifiers, low wavelength blocking sunglasses, etc.). Although Vitamin A shows the tropic and antioxidant effect and protects photoreceptors by reducing the degeneration of photoreceptors, it is suggested not to be given to patients with Retinitis Pigmentosa caused by mutations in the ABCA4 gene. Vitamin E has also been recommended to a few patients, but the use of vitamin E is still questionable; it is suggested that adults with Retinitis Pigmentosa should avoid taking high-dose vitamin E supplements.

These measures are not successful enough to cure the underlying cause of the disease and are generally provided to the affected individuals to delay the disease course. However,  ongoing research states that these measures are not very effective even in even delaying the course of the disease. Hence, it is apparent that the Retinitis Pigmentosa market is very dismal, with no effective therapy approved to date to cure all forms of Retinitis Pigmentosa. One of the major attributed reasons is the poorly understood pathophysiology of Retinitis Pigmentosa.

Nevertheless, one gene therapy, i.e., Spark Therapeutics’ subretinally administered Luxturna (now acquired by Roche), has gained approval during 2019 from the UAE Ministry of Health and Prevention (MoHAP) ^d and Saudi Food and Drug Authority (SFDA) ^e. Luxturna is indicated for treating patients with vision loss due to Leber’s congenital amaurosis (LCA), or Retinitis Pigmentosa inherited retinal dystrophy caused by confirmed biallelic RPE65 mutations. The international media reports the cost of treatment with Luxturna at USD 425,000 (Dh1.56 million) per eye^d. Physicians seem very hopeful about this therapy and believe the therapy’s availability might open doors for more successful gene therapies. Though Luxturna’s medical effectiveness is worth appraising, this therapy has limited use, i.e., for addressing a very rare form of Retinitis Pigmentosa (RPE65-associated Retinitis Pigmentosa; RPE65 mutations account for only 4.4% cases of LCA patients in Saudi Arabia ⁱ).  RPE65-related retinal dystrophy is very rare and reported to affect 1 in 200,000 people worldwide ^j. However, the condition is also more common in the Middle East due to the restricted genetic pool and social preferences for consanguineous marriages.

Clinical trials from major markets like the US and EU are showing great promise. Yet, not much development for newer therapies is visible in the MENA region. However, the high unmet needs associated with Retinitis Pigmentosa could drive vendors to conduct R&D, which could fuel the pipeline for the treatment of Retinitis Pigmentosa. A Phase I trial of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK^f for the MERTK-associated Retinitis Pigmentosa has been performed in Saudi Arabia. Other than that, MD Stem Cells provide bone marrow-derived stem cells (BMSC) for retinal diseases such as age-related macular degeneration (AMD), myopic macular degeneration, hereditary retinopathies such as Retinitis Pigmentosa, cone dystrophy, Stargardts, as well as selected inflammatory, vascular and traumatic conditions ^g. Simultaneously a study to evaluate the use of these autologous bone marrow-derived stem cells (BMSC) to treat retinal and optic nerve damage or disease is being conducted in UAE premises ^h.

Although the efforts put by researchers to develop new approaches to delay or stop the progression of vision deterioration are appreciable, there is still a long way to go. Nevertheless, Retinitis Pigmentosa management in the MENA region shows considerable promise, given the space to develop better treatment approaches to treat all forms of Retinitis Pigmentosa. Continuous efforts can rejuvenate the hopeful and impending occasions regarding approval of drugs that can allow patients to access effective treatment at an affordable cost.

References:

1. Sharonet al. (2015), Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506056/
2. Pandova et al. (2018), Registered blindness in Kuwait – 15 years of dynamic changes https://pubmed.ncbi.nlm.nih.gov/30285528/
3. Al-Merjan et al. (2005), Registered blindness and low vision in Kuwait https://pubmed.ncbi.nlm.nih.gov/16033746/#affiliation-1
4. UAE’s first gene therapy improves eyesight of two Emirati sisters- https://gulfnews.com/uae/health/uaes-first-gene-therapy-improves-eyesight-of-two-emirati-sisters-1.69945550#:~:text=The%20UAE%20Ministry%20of%20Health,%2C%20Luxturna%2C%20in%20June%202019.
5. SFDA Approves Registration of First Gene Therapy to Treat Patients with an Inherited Blindness Caused by Mutations in a Specific Gene- https://old.sfda.gov.sa/en/drug/news/pages/d6-10-2019a1.aspx
6. Clinical Trial in Saudi Arabia: https://www.clinicaltrials.gov/ct2/show/NCT01482195?cond=Retinitis+Pigmentosa&cntry=SA&draw=2&rank=1
7. New Treatment for Blindness Begins in Dubai- Middle East: https://www.einpresswire.com/article/310047764/new-treatment-for-blindness-begins-in-dubai-middle-east
8. Clinical Trial in UAE: https://www.clinicaltrials.gov/ct2/show/NCT03011541?cond=Retinitis+Pigmentosa&cntry=AE&draw=2&rank=1#contacts
9. Li et al. (2009), Mutation Survey of Known LCA Genes and Loci in the Saudi Arabian Population, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695987/
10. Ministry of Health and Prevention Registers an Emerging Gene Therapy Luxturna for Treatment of Inherited Blindness- https://www.mohap.gov.ae/en/MediaCenter/News/Pages/2111.aspx

Source: DelveInsight – www.delveinsight.com