Can Headways in Newborn Screening and Emerging Therapies Revamp the Treatment and Diagnosis of Duchene Muscular Dystrophy (DMD) in the MENA Region?

Duchenne muscular dystrophy (DMD) is a rare and severe X-linked neuromuscular childhood disorder – predominantly present in males  – caused by an absence of dystrophin protein due to mutations of the DMD gene located on the short arm of the X chromosome. Symptoms are usually observed between the ages of 1–6 years, with a majority of the patients becoming nonambulatory by age 13.

The prevalence of DMD in the Middle East, North Africa region is similar to that in other areas of the world, approximately 1 in every 3,600–6,000 live male births. While Saudi Arabia has set the ball rolling by initiating a national registry for neuromuscular diseases, various studies have been conducted in Egypt, Lebanon, Syria, Jordan, Kuwait, Saudi Arabia, and others to understand epidemiological trends in these regions.

Improvement in DMD diagnosis with outstanding progress in newborn screening

The MENA region has taken great strides in DNA extraction and multiplex ligation-dependent probe amplification (MLPA) testing, usually performed locally. However, although genetic diagnostic testing and DMD gene sequencing for identifying specific mutations facilities are partly available, the region has to somewhat rely on the Western countries.

In an initiative to improve the diagnosis rate in the region, Centogene, in 2019, entered into a year-long strategic collaboration with Sarepta Therapeutics to determine patients with DMD. Centogene carried out diagnostic testing using deletion/duplication analysis and full-length sequencing of the DMD gene in MLPA negative (MLPA−) patients. The company also provided CentoCard, Centogene’s proprietary dried blood collection kit, to physicians treating patients with DMD-related symptoms for diagnosing the disease.

Early detection of Duchene Muscular Dystrophy is essential in treating the disease, as starting the treatment at the first opportunity delays the progression of the disease. Newborn screening (NBS) programs are a reasonable solution for increasing the overall diagnosis rate and promoting early DMD diagnosis. Some countries in the region have established NBS programs like the National Neonatal Screening Program in the United Arab Emirates (UAE), launched in January 1995. Currently, every newborn in the country is screened for more than 40 diseases, in addition to congenital heart disease and hearing screening programs. Qatar established a national NBS program in 2003, and the national NBS program in Iran was started in 2004, while the national NBS program in Saudi Arabia was initiated in 2005. Unfortunately, not all countries in the region have NBS programs, and the ones that do might not screen for DMD particularly. However, on the brighter side, this scenario is likely to soon change with the rising awareness about Duchene Muscular Dystrophy in the MENA region. Increasing awareness will shed light on the importance of early DMD diagnosis and treatment in the rest of the areas as well. Moreover, it is expected that the countries such as UAE, Saudi Arabia, Qatar, and Iran, which have an established NBS program in place, would soon include DMD in the list of diseases to be screened and also guide and help the other countries starting their own NBS programs, even at a small scale or as pilot studies.

Current DMD treatments available in the MENA region

Corticosteroids are the current gold standard treatment for Duchene Muscular Dystrophy patients in the region. About 50–80% of DMD patients are maintained on corticosteroids such as prednisone/prednisolone and deflazacort, but different regimens are used, and tolerability may be an issue. Among the approved Duchene Muscular Dystrophy drugs, both PTC Therapeutics’ Translarna (ataluren) and Sarepta Therapeutics’ Exondys 51 (eteplirsen) have been approved in Israel by the Israeli Ministry of Health. Translarna has been shown to slow the disease progression depending on the stage of the disease. It is either given as monotherapy to patients who have been treated with corticosteroids earlier or in combination with corticosteroids.

Various DMD therapies have been approved for in the West in the past few years, but apart from Translarna and Exondys 51, approved only in Israel, no other drugs are available in the MENA region. However, we have high hopes that newer and improved Duchene Muscular Dystrophy therapies in the market, including the Duchene Muscular Dystrophy pipeline, will eventually make their way to the MENA region and provide multiple and better-treated options to doctors and patients alike. In fact, based on the stronghold of Sarepta’s Exondys 51 in Israel, we expect Sarepta’s other approved exon-skipping therapies – Vyondys 53 and Amondys 45 – to enter the country soon.

DMD Emerging therapies in the MENA region

In the last decade, companies have had a lot of growing interest in developing novel therapeutic approaches for treating DMD and delaying its progression. Key players such as Pfizer (PF-06939926), Fibrogen (pamrevlumab), Santhera Pharmaceuticals/ReveraGen BioPharma (vamorolone), Sarepta Therapeutics (casimersen, golodirsen), Italfarmaco (givinostat) have already conducted or are currently conducting clinical trials for their respective therapies for DMD in Israel. We expect a geographical expansion covering other regions as well.

The current scenario of Duchene Muscular Dystrophy in the MENA region is adequate and better in some countries – Israel, UAE, Saudi Arabia, etc. – than others. Nevertheless, the diagnosis rate is expected to increase with a greater understanding and awareness about DMD in the MENA region. At the same time, the national NBS programs will help in early DMD diagnosis, allowing patients to start their treatment on time. With the introduction of standard guidelines for managing DMD, the overall diagnosis and treatment are expected to drastically improve, providing better and holistic care for the patients. Moreover, initiatives by the government to improve the market access scenarios of their respective countries and encourage companies to enter their domain for clinical trials and selling therapies will also help vastly in advancing the current scenario of DMD in the region. We also believe that providing good insurance coverage to the patients by the government regulatory bodies in the MENA region can allow them to afford some of the expensive and effective treatment options. In addition, providing services including respiratory, cardiac, and physiotherapy expertise will also go a long way to ensure the patients’ quality of life.

Awareness about DMD plays a vital role in improving the scenario around the disease, especially when we have mutation-specific therapies in the market now, which can be a boon for the MENA region as well. However, to have other exon-skipping therapies as well as gene therapies developed and approved in the region, authorities need to shift focus towards standardized referral patient registries and support groups that will significantly improve the management of the disease

There are isolated patient support groups in the MENA region, but the role of patient advocacy is limited. The governments must take initiatives to provide ongoing education through different channels such as local language family guides on how to deal with the disease and online portals in Arabic, which will empower patients and their families and help reduce the social stigma associated with diseases like Duchene Muscular Dystrophy.

References:

1. Alghamdi, F., Al-Tawari, A., Alrohaif, H., Alshuaibi, W., Mansour, H., Aartsma-Rus, A., & Mégarbané, A. (2021). Case Report: The Genetic Diagnosis of Duchenne Muscular Dystrophy in the Middle East. Frontiers in Pediatrics, 9. https://doi.org/10.3389/FPED.2021.716424/FULL
2. Bamaga, A. K., Alghamdi, F., Alshaikh, N., Altwaijri, W., Bashiri, F. A., Hundallah, K., Abukhaled, M., Muthaffar, O. Y., Al-Mehmadi, S., Jamaly, T. A., Al-Muhaizea, M. A., & Al-Saman, A. (2021). Consensus Statement on the Management of Duchenne Muscular Dystrophy in Saudi Arabia During the Coronavirus Disease 2019 Pandemic. Frontiers in Pediatrics, 9, 65. https://doi.org/10.3389/FPED.2021.629549/BIBTEX
3. (n.d.). Join LAND for Hope: a support group for Duchenne Muscular Dystrophy patients in the MENA region – Genpharm. Retrieved December 13, 2021, from https://www.genpharmservices.com/join-land-for-hope-a-support-group-for-duchenne-muscular-dystrophy-patients-in-the-mena-region-2/
4. Goemans, N., Kirschner, J., & Mercuri, E. (2014). New Perspectives in the Management of Duchenne Muscular Dystrophy. Undefined, 9(1), 78–82. https://doi.org/10.17925/ENR.2014.09.01.78
5. Jumah, M. Al, Muhaizea, M. Al, Rumayyan, A. Al, Saman, A. Al, Shehri, A. Al, Cupler, E., Jan, M., Madani, A. Al, Fathalla, W., Kashyape, P., Kodavooru, G., Thihli, K. Al, Bastaki, L., Megarbane, A., Skrypnyk, C., Zamani, G., Tuffery-Giraud, S., Urtizberea, A., & González, C. I. O. (2019). Current management of Duchenne muscular dystrophy in the Middle East: expert report. Neurodegenerative Disease Management, 9(3), 123. https://doi.org/10.2217/NMT-2019-0002
6. Krotoski, D., Namaste, S., Raouf, R. K., El Nekhely, I., Hindi-Alexander, M., Engelson, G., Hanson, J. W., & Howell, R. R. (2009). Conference report: Second conference of the Middle East and North Africa newborn screening initiative: Partnerships for sustainable newborn screening infrastructure and research opportunities. Genetics in Medicine 2009 11:9, 11(9), 663–668. https://doi.org/10.1097/gim.0b013e3181ab2277
7. (n.d.). LaboShop. Retrieved December 13, 2021, from https://laboshop.ae/product/dmd-pcr-857
8. Muscular Dystrophy. (2019). Collaboration Seeks to Identify DMD Patients in Middle East, North Africa. https://musculardystrophynews.com/2019/03/04/collaboration-identify-dmd-patients-middle-east-north-africa/
9. (n.d.). Novartis Pharmaceuticals | Novartis. Retrieved December 13, 2021, from https://www.novartis.com/about/innovative-medicines/novartis-pharmaceuticals
10. Skrinska, V., Khneisser, I., Schielen, P., & Loeber, G. (2020). Introducing and Expanding Newborn Screening in the MENA Region. International Journal of Neonatal Screening 2020, Vol. 6, Page 12, 6(1), 12. https://doi.org/10.3390/IJNS6010012
11. Therrell, B. L., Padilla, C. D., Loeber, J. G., Kneisser, I., Saadallah, A., Borrajo, G. J. C., & Adams, J. (2015). Current status of newborn screening worldwide: 2015. Seminars in Perinatology, 39(3), 171–187. https://doi.org/10.1053/J.SEMPERI.2015.03.002
12. Urtizberea, J. A. (2020). Neuromuscular Disorders in the Middle East: A -20 year Personal Journey. 2020(2), 6. https://doi.org/10.5339/QPROC.2020.NMD.6

Source: DelveInsight – www.delveinsight.com