Spinal Muscular Atrophy: Why Early Diagnosis And Treatment Is Crucial For Patients

SMA Type 1, the most common and most severe, develops in babies less than 6 months old. 68% of the Type 1 SMA children die before the age of 2 and 82% die before the age of 4

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New Delhi: Over the years, the unmet needs of patients with Spinal Muscular Atrophy (SMA) has increased manifold. Caused by deficiency of survival motor neuron (SMN) protein, this rare neuromuscular disorder affects nearly one in 10,000 live births globally and one in 7,744 live births in India, and is the most common genetic cause of death in infants.

SMN protein, which is found throughout the body, plays a vital role in motor function. In SMA patients, the deficiency in SMN protein is a result of mutation of the SMN1 gene, which leads to progressive destruction of motor neurons, which then leads to progressive weakness of the muscles. 

As muscles weaken over time, patients struggle to perform routine activities including everyday activities like sitting, swallowing, or walking. For the severe type of SMA, even normal breathing becomes a challenge.

Importance of early diagnosis and treatment

SMA patients and their families navigate through several challenges during their journey to seek diagnosis and suitable treatment. Several clinical trials on SMA patients have indicated that efficacy of treatment is better if the diagnosis is early.

There are 5 main SMA Types, classified as SMA 0, SMA I, SMA II, SMA III and SMA IV.

SMA Type 1 develops in babies less than 6 months old and can severely deteriorate muscle strength rapidly. It is the most common and severe type of SMA, and 68% of the Type 1 SMA children die before the age of 2 and 82% die before the age of 4. 

Type 2 SMA children suffer severe morbidity and face difficulty in walking or standing on their own. Delayed treatment can have a crippling impact on patients and their families.

Untreated children with SMA can lose the majority of their motor neurons, responsible for controlling movement of arms, legs, chest, face, throat, and tongue. They often need external breathing support and develop respiratory compromise. As the condition progresses untreated, they develop scoliosis and repeated episodes of pneumonia. 

Preventing diagnostic delays will enable early institution of treatment and increase the chance of improved motor development and survival of babies living with this debilitating condition.

To expedite diagnosis, education and awareness are equally necessary. Paediatricians, other allied health care professionals and caregivers should be aware about the early signs and symptoms of SMA. This could help families to seek treatment on time and plan for a holistic multidisciplinary treatment along with their pediatrician.

The success of treatment of SMA will depend upon beginning treatment early, before potentially irreversible motor neuron loss and associated progressive complications develop. Particularly in the more severe types, the window for beneficial treatment outcomes is very narrow and early initiation is needed to maximise the benefit of treatment.

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SMA management

Significant motor development and prolonged survival can be achieved with the current advanced treatment options available for SMA. Starting therapy at an early age can positively impact not only the patients’ quality of life but also their caregiver’s. The goals of treatment in the most severe form of the disease are survival and gaining motor milestones. In less severe forms of the disease, treatment aims to help patients with SMA perform activities of daily living.

For a long time, patients with SMA faced treatment barriers as none of the approved treatment options were available in India. At present, only 3 approved treatments exist for SMA, namely Evrysdi (Risdiplam), Spinraza (Nusinersen) and Zolgensma (Onasemnogene aboparvovec). All three of them have been or are being administered to many patients across India through humanitarian access programmes for the last two years, but the number of recipients is very limited. Among these, only Evrysdi is approved and being marketed in India currently. With Evrysdi (Risdiplam), SMA patients in India have a new hope for fighting SMA and overcoming associated challenges.

• Evrysdi is an oral daily administered medication and is currently the only available therapy in India. It has been approved for infants above 2 months of age. It constitutes a ray of hope for the SMA community including caregivers and paediatricians. Depending on the disease severity, Evrysdi can result in functionally meaningful motor milestone improvement in infants with SMA type 1. It can improve motor function and can potentially enable activities of daily living in children, teenagers and adults after even one year of treatment
• Zolgensma is an adeno-associated virus vector-based gene therapy indicated for the treatment of SMA patients less than two years of age. It Is a one-time intravenous infusion The therapy has shown to offer meaningful therapeutic benefits to patients with SMA
• Nusinersen is a disease-modifying treatment for all types of SMA. It allows the body to produce more functional SMN protein from the SMN2 gene. It is given intrathecally (CSF space in the spinal canal) as four loading doses, first three at interval of 14 days and 4th dose 30 days after the 3rd dose followed by four monthly life-long maintenance doses. It was the first therapy approved by the US FDA in December 2016. Data from clinical trials showed that it is a well-tolerated drug leading to significant improvement in motor skills after 3 months of initiation of therapy

It is important to note that suitable therapy options should be decided under the treating pediatricians’s discretion only. The prohibitive cost of these medications is a challenge for LMICs like ours.

Management of SMA should have a multidisciplinary approach. Holistic treatment should be followed including nutritional counselling, physiotherapy, respiratory and other supportive care.

Early treatment and care can decrease the rate of disease progression and significantly improve the quality life as well as clinical outcomes of patients living with Spinal Muscular Atrophy.

Prof. Sheffali Gulati is Faculty-in-charge, Center of Excellence and Advanced Research on Childhood Neurodevelopmental Disorders, and Chief, Child Neurology Division, Department of Paediatrics, AIIMS, New Delhi.