Spinal Muscular Atrophy awareness: Treatment advances offer hope to SMA patients

Spinal Muscular Atrophy or SMA is a life-altering rare disease, which has a crippling impact on the life of a patient.Here are some global statistics that highlight this:

• Typically diagnosed in childhood, SMA affects approximately 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.
• Sixty percent of SMA patients born each year suffer from Type 1 SMA. All these children require assistance for sitting. In the natural course of the disease, 68% die before their second birthday and twenty-nine percent of children are alive without permanent ventilation at 14 months of age.
• Twenty-nine percent of kids born with SMA Type 2 suffer severe muscle weakness and cannot even stand on their own.

SMA can rob a child of the chance to live a normal, healthy life before it has really begun. It is a rare inherited neuromuscular disorder characterized by loss of motor neurons in the spinal cord due to a mutation in the SMN1 (Survival Motor Neuron 1) gene.It manifests in early to late infancy, depending on genotype with motor predominant developmental delay, progressive weakness of all four limbs, wasting and respiratory involvement.Five clinical phenotypes of SMA are recognized: SMA 0, SMA I, SMA II, SMA III and SMA IV.Potential complications include bone fractures, hip dislocation and scoliosis (curvature of the spine), malnutrition and dehydration due to problems with eating and swallowing and many develop significant respiratory and breathing problems.

Globally, only 3 approved treatments exist for SMA, namely Evrysdi (Risdiplam), Spinraza (Nusinersen) and Zolgensma (Onasemnogene aboparvovec).Of these, until recently none were available in India. They have been available in the country for the last two years as a part of humanitarian access programs.

• Nusinersen (Spinraza) is a disease-modifying treatment by Biogen for all types of SMA. It was the first therapy approved by US FDA in December 2016. It is an antisense oligonucleotide that allows the body to produce more functional SMN protein from the SMN2 gene. 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 given intrathecally (CSF space in the spinal canal) as four loading doses at two weeks intervals followed by four monthly life-long maintenance doses.
• The US FDA has approved Zolgensma (Onasemnogene abeparvovec) in May 2019 for the treatment of SMA. It is an adeno-associated virus vector-based gene therapy indicated for the treatment of SMA patients less than two years of age with SMA, with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. European Medicines Agency (EMA) also approved the drug in March 2020. Studies have shown promising results. The dosage is determined by the patient’s body weight, which is given as a single time intravenous infusion over one hour.
• Evrysdi (Risdiplam) received USFDA approval in August 2020 for children two months of age or older. It was launched by Roche in India in July 2021. With its launch, a huge unmet need has been fulfilled for the entire SMA community including caregivers and medical practitioners. Evrysdi (Risdiplam), is a survival motor neuron-2 (SMN2) splicing modifier for SMA and is an orally (by mouth or by feeding tube) administered liquid. Evrysdi is designed to treat SMA by increasing and sustaining functional levels of the SMN protein throughout the central nervous system and peripheral tissues through daily dosing. The dosage is determined by the patient’s body weight. This compound is undergoing four pivotal trials worldwide– FIREFISH, SUNFISH, JEWELFISH and RAINBOWFISH, which has shown promising results for the treatment of patients in all ages and stages of SMA. Its safety profile is also well established.

The costs of all these medications are prohibitive. All these medicines except Evrysdi (Risdiplam) are awaiting DCGI approval in India.The conversation about SMA in our country has been confined to the challenges of exorbitant pricing, access and affordability of such drug therapies. It is important that we also focus on the psychosocial impact of the disease and remember that a multidisciplinary approach is a mainstay to better manage the disease, which encompasses nutritional counselling, physiotherapy, respiratory and other supportive care.The availability of the right information from specialists is critical for making the road to diagnosis and treatment for SMA patients more accessible. However, it is necessary that the patients and their caregivers consult with their healthcare provider before beginning treatment.The author is the Faculty-in-charge, Center of Excellence and Advanced Research on Childhood Neurodevelopmental Disorders, Chief, Child Neurology Division, Department of Pediatrics, AIIMS, New Delhi.