What is
SMA.
A rare genetic disorder that causes progressive muscle wasting by affecting the motor nerve cells in the spinal cord, taking away the ability to walk, eat or even breathe.
When muscle
are WEAK.
“Darling, do you notice that our baby is inactive?”
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“Mom, why I am so tired?! My legs are so heavy!”
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“Daddy, why can’t I raise my hand higher or carry heavy things?”
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These alarming questions may have been asked by our relative or someone else that we know. These symptoms may not always be due to spinal muscular atrophy (SMA), but they are common experiences for those suffering from this genetic disorder.
GENETIC disease.
SMA is a disorder that gradually takes away an individual’s physical abilities as there is a loss of the motor neurons – specialised nerve cells that are mainly located in the spinal cord, which control the body’s muscles.
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It occurs when a baby inherits two faulty copies of a gene called the Survival of Motor Neuron 1 (SMN1) gene – one from each of his or her parents.
(see image below)
When a baby inherits two faulty copies of a gene called the Survival of Motor Neuron 1 (SMN1) gene – one from each of his or her parents. In a healthy person, this gene produces a protein essential for the functioning of motor neurons. In SMA patients, this protein is lacking due to the abnormality of their SMN1 genes.
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The affected nerve cells cannot function correctly, and in the end, will stop functioning altogether, leading to devastating, and often deadly, muscle weakness and wasting (atrophy). The ability to crawl, sit, walk, control head movements, eat and breathe are all affected.
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Some patients may also experience an abnormal curvature of their spine called scoliosis, caused by weakness of their abdominal muscles.
SMA is the main hereditary reason for the death of newborns, most often due to their inability to breathe. The survival of affected individuals is actually dependent on the number of copies they have of another gene known as SMN2.
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Usually called the back-up gene for SMN1, SMN2 typically produces unstable SMN proteins, which are unable to fold into a functional shape. Only 10% of the proteins produced by SMN2 actually function properly. (see image below)​
The number of SMN2 genes vary from person to person, and are an indication of how severe the SMA is in each patient. The less the number of SMN2 genes a patient has, the more severe his or her symptoms will be.
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It is important to note that SMA does not influence an individual’s capacity to think, learn or build relationships with others.
1 in 4 CHANCE.
SMA can affect any race or gender. In America, SMA affects approximately one in 10,000 babies, with about one in every 50 Americans being a genetic carrier. However, the prevalence of SMA in Malaysia is unknown.
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Given the high frequency estimated from other countries, one can expect to observe a significant number of SMA individuals and carriers in Malaysia too. If the estimated prevalence above applies, there may be 3,200 SMA-affected individuals and 640,000 SMA carriers in our Malaysian population of 32 million.
SMA is described as an autosomal recessive disorder. This means that there is a one in four chance of conceiving an SMA-affected baby, if both the father and mother are carriers.
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Genetic counselling and testing for couples are essential for family planning. This may help decrease, or at least, not increase the frequency of SMA. Plus early, accurate screening for newborn babies is essential in starting early treatment to decrease the severity of the symptoms and improve chances of survival.
EXPENSIVE treatments.
December 2016 was a very long-awaited moment for SMA patients and their families when the US Food and Drug Administration (FDA) announced the approval and licensing of nusinersen, the first drug to treat SMA.
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Nusinersen helps the SMN2 gene produce more functional SMN proteins, allowing more motor neurons to stay alive and prevent the weakening and wastage of the body’s muscles. However, this drug’s effects are not permanent, requiring it to be taken as long as the patient lives.
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The real challenge is the high price of the drug, which makes it unaffordable to all except the very affluent. Nusinersen costs approximately US$125,000 (RM526,000) per dose. With SMA patients recommended to take four doses per year, this means an annual cost of US$750,000 (RM3,050,800).
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In May 2019, another treatment for SMA was approved by the US FDA. Onasemnogene Abeparvovec is the first gene therapy treatment to treat SMA patients less than two years old through a single intravenous (IV) injection.
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This therapy replaces the function of the faulty SMN1 gene, enabling sufficient SMN protein to be produced for the body’s needs. It also raises a liver enzyme (serum aminotransferase) to a potentially harmful level, but this can be controlled using prednisolone, a commonly-used steroid medication.
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Increasingly, new drugs amass huge costs during their development and this is reflected in the price of onasemnogene abeparvovec. This one-off treatment costs US$2.125 million (RM8.94 million) for one injection, making it the most expensive drug in the world, according to a Bloomberg report.
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Given that neither nusinersen nor onasemnogene abeparvovec is currently available in Malaysia and their huge cost, perhaps supportive treatment via multidisciplinary palliative care is a more realistic option to help maintain the quality of life of Malaysian SMA patients.
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Early diagnosis and investigations, such as respiratory muscle function studies, cough effectiveness, swallow test, physical and occupational therapy assessments, assistive equipment evaluation, and x-rays of the hip and spine, are essential in the initial overall assessment of SMA patients.
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These may determine the most suitable treatments and aids for each patient, such as physiotherapy, assisted coughing, wheelchair use, bracing, spinal surgery, and nutritional and food supplements.
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Maximising the potential of SMA patients and minimising their disabilities enables and promotes their independence at each phase of the illness, optimises their quality of life and may help slow their disease progression.
Siti Safura Jaapar is a PhD candidate studying the role of the gut microbiome in SMA at Perdana University. She is also the founding president of Spinal Muscular Atrophy Malaysia and an SMA patient.
This article is courtesy of Perdana University.
