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#apaperaday: Gene Therapy for Duchenne Muscular Dystrophy: Unlocking the Opportunities in Countries in the Middle East and Beyond

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Gene Therapy for Duchenne Muscular Dystrophy: Unlocking the Opportunities in Countries in the Middle East and Beyond

Today’s pick is from Journal of Neuromuscular Diseases by Elbashir et al on gene therapy opportunities for Duchenne in the Middle East doi 10.3233/JND-221528

Duchenne is a rare muscle wasting disease that requires multidisciplinary care. Therapies to replace the missing protein (dystrophin) are in development. To study how prepared the Middle East is for gene therapy for Duchenne an expert meeting was organized (sponsored by Pfizer)

The meeting involved a limited number of individuals from the United Arab Emirates (UAE) and Kuwait. However, as pointed out by the authors, only a limited number of health care professionals in these countries has expertise with caring for Duchenne patients.

Authors outline the healthcare system in the countries. Both countries have many non-nationals. In UAE there are government-funded hospitals (free for nationals and non-nationals) and private hospitals (for which you have to pay or your insurance has to pay if they cover this).

In Kuwait the healthcare system is free for nationals, but non-national residents have access via an insurance card (involving an annual fee). Authors first discussed the journey to diagnosis, stressing that lack of awareness leads to delays and diagnostic odysseys.

If there is a family history, things generally go relatively quick. Lacking a family history many unnecessary work-up is done including X-rays, liver investigations etc. CK is not measured regularly and therefore increased transaminases are thought to mark a liver problem.

Authors estimate a diagnostic delay of 1-2 years lacking a family history. In both countries about 2-5 new patients are diagnosed per year (national and non-national). Once they are referred to an expert center, diagnosis is quick.

Authors stress that when gene therapy would become an option, earlier diagnosis would be better. I’ll add reasons: smaller means less viral particles so less risks, younger means less accumulated muscle damage and less risk of having AAV antibodies.

Authors outline that in UAE a healthcare reform is taking place which should improve time to diagnosis. The majority of patients is currently diagnosed between 3 and 6 years – however, 25% is diagnosed between 6 and 9 (while starting steroids ideally is done at 4-5 years).

Authors stress that doing more CK tests would help to flag earlier that patients have a muscle wasting diseases and would reduce time to diagnosis. Genetic testing is free for everyone in Kuwait and for nationals in UAE. In Kuwait they do MLPA and then NGS when MLPA is negative.

UAE does not have a patient registry. In Kuwait there are 139 Duchenne patients (46 non nationals) – the ones formally diagnosed. Steroid treatment is part of the standards of care, but started late in many patients due to late diagnosis or reluctance of clinicians & families

Authors stress the need for education of everyone about the need for steroids. Exon skipping drugs are becoming available in both countries as well. Authors point out that multidisciplinary care is challenging in both countries. It is often fragmented over hospitals.

Sustainability is challenging as is transition to adult care. Both countries are working on improving care however, in UAE with the healthcare reform and in Kuwait they plan a single center of expertise for Duchenne. A hub and spoke model would be best.

Finally, authors discussed how ready the countries are for AAV gene therapy. Many hospitals involved in Duchenne care have experience with gene therapy for other diseases. However, increased awareness for clinicians and families is needed for AAV gene therapy for Duchenne.

e.g. families need to understand that micro-dystrophin is not a cure and clinicians need to understand the risks involved. Also logistic matters arose, e.g. AAV antibody tests are done in the USA and Europe, but patients need to be infused <2 weeks after test results.

A personal addition: what about the percentage of AAV positive individuals in the Middle East? We know there are geographic differences for that – would be best to study this now. Authors conclude that planning and education are needed.

I agree and I appreciate that they include patient education in the things that need to be done. Given the costs of gene therapies authors also outline that financial models need to be discussed to cover this within the healthcare system of the Middle East.

All in all I like the paper and the proactive approach the authors had. While the work/meeting was sponsored by Pfizer – who are developing gene therapy for Duchenne, it is clear that the work had an impact beyond just ‘how ready are these countries for gene therapy’

Better education and raised awareness will benefit the patients regardless of whether they are eligible for gene therapy. Furthermore, the self reflection of the experts will likely improve how they do things in their hospitals as well.