Sheffali GulatiAug 11, 2021 12:30:21 PM
Spinal muscular atrophy, or SMA, is a life-changing rare disease that is debilitating in a patient’s life.
Here are some global statistics that highlight:
- Typically diagnosed in childhood, SMA affects approximately one in 10,000 live births worldwide and one in 7,744 live births in India and is the leading genetic cause of infant death.
- Sixty percent of SMA patients born each year have type 1 SMA. All of these children need a sitting aid. In the natural course of the disease, 68% die before their second birthday and 29% of children at the age of 14 months live without permanent ventilation.
- Twenty-nine percent of children born with SMA type 2 have severe muscle weakness and cannot even stand on their own.
SMA can rob a child of a normal, healthy life before they have really started. It is a rare hereditary neuromuscular disorder characterized by the loss of motor neurons in the spinal cord due to a mutation in the SMN1 (survival motor neuron 1) gene.
It manifests itself in early to late infancy, depending on the genotype with predominantly motor developmental retardation, progressive weakness in all four limbs, emaciation and involvement of the respiratory tract.
Five clinical phenotypes of SMA are recognized: SMA 0, SMA I, SMA II, SMA III, and SMA IV.
Possible complications are broken bones, hip dislocation and scoliosis (curvature of the spine), Malnutrition and dehydration due to difficulty eating and swallowing, and many develop significant breathing and breathing problems Difficulty breathing.
Need better awareness in India
In India, the delay in diagnosing SMA is due to a limited number of laboratories performing genetic diagnostic studies and low disease awareness. Parents get a second, third, or even fourth medical opinion from various specialists, which means that fewer treatment options are found as the disease progresses. Therefore, it is crucial to raise awareness among specialists such as pediatricians and neurologists to identify early signs of the disease such as delayed or lethargic developmental milestones.
Timely diagnosis and therapy initiation can help infant SMA patients survive and have a significantly better quality of life by removing motor milestones such as unassisted sitting, rolling on your side, assisted standing, ability to swallow, and other such motor functions as defined by the quantitative scale of the motor function measurement.
Treatments for SMA
There are only 3 approved treatments for SMA worldwide, namely Evrysdi (Risdiplam), Spinraza (Nusinersen) and Zolgensma (Onasemnogene aboparvovec).
None of these were available in India until recently. They have been available to the country for two years through humanitarian access programs.
- Nusinersen (Spinraza) is a disease-modifying treatment from Biogen for all types of SMA. It was the first therapy to be approved by the US FDA in December 2016. It’s an antisense oligonucleotide that allows the body to make a more functional SMN protein from the SMN2 gene. Data Clinical studies have shown that it is a well-tolerated drug that leads to a significant improvement in motor skills after starting therapy for 3 months. It is administered intrathecally (CSF space in the spinal canal) as four loading doses two weeks apart, followed by four monthly lifelong maintenance doses.
- The US FDA has authorized Zolgensma (Onasemnogene abeparvovec) in May 2019 for the treatment of SMA. It is an adeno-associated virus-vector-based gene therapy, which is indicated for the treatment of SMA patients under two years of age with SMA with bi-allelic mutations in the survival motor neuron 1 gene (SMN1). The European Medicines Agency (EMA) also approved the drug in March 2020. Studies have shown promising results. That dosage is determined by the patient’s body weight, which is given as a single intravenous infusion over an hour.
- Evrysdi (Risdiplam) received USFDA approval for children two months and older in August 2020. It was launched by Roche in India in July 2021. Its launch met a huge unmet need for the entire SMA community, including nurses and physicians. Evrysdi (Risdiplam) is a survival motor neuron-2 (SMN2) splice modifier for SMA and is a fluid given orally (by mouth or through a feeding tube). Evrysdi was designed to Treat high school by increasing and maintaining functional levels of SMN protein throughout the central nervous system and peripheral tissues through daily dosing. The dosage depends on the Body weight of the patient. This compound is undergoing four pivotal studies worldwide – FIREFISH, SUNFISH, JEWELFISH and RAINBOWFISH, which have shown promising results for the treatment of patients of all ages and stages of SMA. Its safety profile is also well established.
The cost of all of these drugs is prohibitive. All of these drugs with the exception of Evrysdi (Risdiplam) are awaiting DCGI approval in India.
The discussion about SMA in our country has been limited to the challenges of exorbitant prices, accessibility and affordability of such drug therapies. It is important that we also focus on that psychosocial effects the disease and remember that a multidisciplinary approach is a cornerstone of better treatment for the disease, which includes nutritional counseling, physical therapy, ventilation and other supportive measures.
Having the right information from specialists is critical to making the path to diagnose and treat SMA patients more accessible. However, it is required that patients and their caregivers consult with their healthcare provider before starting treatment.
The author is the responsible faculty, Center of Excellence and Advanced Research on Childhood Neurodevelopmental Disorders, Chief, Child Neurology Division, Department of Pediatrics, AIIMS, New Delhi.
