In our recent podcast interview, Dr. Omendra Narayan, Consultant Interventional Paediatric Pulmonologist & Sleep Physician at American Hospital Dubai, talked about ground-breaking research into SMA gene therapy for Spinal Muscular Atrophy that he has been involved with. The research, carried out in Dubai, was a collaboration between expert physicians from American Hospital Dubai, Medcare Women and Children Hospital, Dubai Health, and Mediclinic City Hospital.
Associate Professor Dr. Omendra Narayan is a Consultant Paediatric Pulmonologist, UK board-certified with dual CCT in Pediatrics and Pediatric Pulmonology. Dr. Omendra relocated to American Hospital Dubai in July 2021 to set up a new Paediatric Pulmonology service. He is also a Director of the American Children’s Centre, a Paediatric Specialist facility within American Hospital Dubai.
Research into Gene Therapy for Spinal Muscular Atrophy in Dubai
Dubai has an excellent healthcare system that has expanded and developed remarkably over recent decades. Aside from providing world-class medical services for both Emirati citizens and expatriate residents, the number of highly impactful clinical research projects in Dubai continues to grow, supported by both private and public sector hospitals and other research institutions.
A recent research project carried out in Dubai analysed the outcomes and safety of a relatively new gene therapy for a rare condition called Spinal Muscular Atrophy. Research into onasemnogene abeparvovec therapy was carried out in a collaboration between paediatric neurologists, pulmonologists, and other specialists from Medcare Women and Children Hospital, American Hospital Dubai, Dubai Health, University of Sharjah College of Medicine, and Mediclinic City Hospital.
What is Spinal Muscular Atrophy?
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease. In individuals with SMA, a lack of SMN protein, essential for maintaining the health and normal function of motor neurons, causes the loss of motor neurons in the spinal cord that control muscle movement, leading to progressive muscle weakness and atrophy. In most cases, Spinal Muscular Atrophy is inherited when both biological parents carry one copy of a mutated SMN (survival motor neuron) gene that encodes for SMN protein.
Spinal muscular atrophy is classified into 5 types according to severity. About 60% of SMA cases are type 1, or severe Spinal Muscular Atrophy (also called Werdnig-Hoffman disease). The progressive weakness and wasting of various muscle groups may cause difficulties with breathing, swallowing, eating, speaking, sitting up, crawling, and walking.
How common is Spinal Muscular Atrophy?
Although relatively rare, Spinal Muscular Atrophy is the second most common severe hereditary disease of infancy and childhood, after cystic fibrosis. The incidence of SMA ranges from 1 per 6000 to 11,000 live births worldwide. The reported incidence of Spinal Muscular Atrophy in the Middle East is 40 times higher than in the Western Pacific region, attributed to higher consanguinity rates. Spinal Muscular Atrophy is not preventable, but carrier testing and genetic counseling may be available for couples planning to start a family.
What treatment is currently available for Spinal Muscular Atrophy (SMA)?
Currently, there is no definitive cure for SMA, with previous treatments mostly aimed at managing symptoms and preventing complications. The prognosis depends on the subtype of the disease and access to treatment, with respiratory support especially crucial. Patients with Spinal Muscular Atrophy require a multidisciplinary team to provide physical therapy, ventilation, feeding and swallowing support, speech therapy, occupational therapy, and assistive devices as required. Current treatments also include Risdiplam – an oral medicine which can increase SMN protein levels in the blood, and Nusinersin delivered via intrathecal injections into the cerebrospinal fluid, to help increase SMN protein levels.
Gene therapy, a relatively new development that is still undergoing research, is already showing promising results, giving hope to families affected by SMA.
What is Onasemnogene abeparvovec therapy?
Onasemnogene abeparvovec is a ground-breaking new gene therapy. It utilises an adenovirus-associated viral vector to deliver a functional copy of the human survival motor neuron (SMN) gene, to replace a missing or faulty SMN gene, which is the cause of Spinal Muscular Atrophy.
Onasemnogene abeparvovec therapy is given by a one-time intravenous (IV) infusion. Corticosteroids are also given to suppress the body’s immune response to the gene therapy. Onasemnogene abeparvovec therapy first gained approval for the treatment of paediatric patients under two years of age in the United States in 2019 and has been offered for carefully selected patients at tertiary centres in the UAE since 2020. Early intervention leads to better outcomes.
Previous clinical trials have shown that gene therapy may be particularly effective if started early, even before symptoms of SMA appear. However, gene therapy is a precision treatment that is expensive and often not covered by medical insurance.
Gene therapy for Spinal Muscular Atrophy in Dubai
Dubai is a regional ‘hub’ for gene therapy treatment for Spinal Muscular Atrophy. Onasemnogene abeparvovec therapy is currently available at 4 centres in Dubai: American Hospital, Al Jalila Children’s Hospital, Medcare Women and Children Hospital, and Fakeeh University Hospital. Patients travel from Turkey and from other countries in the Middle East, South Asia, and North and East Africa for treatment. Crowdfunding may be used to cover the costs for some patients. Where newborn screening has not been available, some patients have been diagnosed relatively late and may have more profound muscle weakness and respiratory issues requiring ventilatory support.
Patients with spinal muscular atrophy type 1 (SMA-1) requiring invasive ventilation can be eligible for gene therapy if they tolerate at least 8 hours off ventilation per day. More countries are introducing newborn screening. For example, Turkey implemented nationwide newborn screening 2 years ago, enabling doctors to diagnose children earlier and intervene more effectively.
How was the research in Dubai carried out?
The research was carried out at Medcare Women and Children Hospital, in collaboration with expert physicians and researchers from the other treatment centres in Dubai. A prospective cohort study published in Advances in Respiratory Medicine followed outcomes for gene therapy given to 22 patients (11 male and 11 female) with Spinal Muscular Atrophy type 1 (SMA-1) who were receiving ventilation via tracheostomy. The patient profile at the centre meant that, compared to previous studies in other countries, there were more patients receiving intensive gene therapy at a relatively late age, with a mean of 29.2 (SD: 17.1) months.
A second study published in Muscle and Nerve retrospectively analysed short-term outcomes for a total of 60 patients with Spinal Muscular Atrophy (46 SMA-1, and 14 with SMA-2). The age of the patients ranged from 7 months to just under 7 years, with a mean age of 29.6 months. In this cohort, 47% of children were receiving intensive ventilatory support via tracheostomy, and 28% non-invasive Bilevel Positive Airway Pressure (BiPAP). For this study, outcomes were recorded for 3 months only, as the majority of patients returned to their home countries after this time. Comprehensive clinical evaluations, including assessment of motor function and monitoring for side effects of treatment, were carried out at baseline and 3 months following gene therapy.
What were the main results of the research?
In the prospective study, gene therapy was found to be safe and effective even for the older patients. 11 patients had reduced hours on ventilation, and 1 patient was completely weaned off the ventilator 8 months after gene therapy.
In the retrospective study, all children demonstrated marked improvements in motor function within 3 months after gene therapy. Children with intensive ventilatory support via tracheostomy also demonstrated increased ventilator-free intervals, reduced antibiotic dependency, and fewer hospital admissions. The use of gene therapy also showed good short-term safety in this study. Nonetheless, long-term follow-up data remains imperative for a more comprehensive understanding of the therapy’s lasting impact.
What does this mean for children with Spinal Muscular Atrophy (SMA)?
While early diagnosis and promotion of newborn screening will benefit patients with SMA, this research shows that older patients with SMA-1 still have a chance for improvement if presented late for gene therapy. High-quality clinical care for children with SMA is vital and should be paired with gene therapy management.
Are there plans for further research in this area?
Research into gene therapy for Spinal Muscular Atrophy will continue in different countries. In the UAE, there are future plans to carry out further research involving a larger number of patients. Doctors in the UAE have already administered gene therapy for Duchenne Muscular Dystrophy to more than 10 children, demonstrating similar success with other genetic conditions.
The healthcare sector in the UAE is very supportive of clinical research. Many hospitals have active ethics and research committees, and researchers from different hospitals collaborate for the benefit of patients. It is anticipated that more cutting-edge research will be published out of the UAE in the near future.
References:
Alajjuri MA, Abusamra R, Mundada V, Narayan O. Real-World Data in Children with Spinal Muscular Atrophy Type 1 on Long-Term Ventilation Receiving Gene Therapy: A Prospective Cohort Study. Advances in Respiratory Medicine. 2024; 92(5):338-347. https://doi.org/10.3390/arm92050032
Mundada V, Narayan O, Arora S, et al. Onasemnogene abeparvovec gene therapy for spinal muscular atrophy: A cohort study from the United Arab Emirates. Muscle & Nerve. 2024; 70(4): 808-815. doi:10.1002/mus.28222
