ABOUT SPINAL MUSCULAR ATROPHY (SMA) – TYPES, CAUSE AND CURE

• Type 1 is the most severe and is diagnosed in the first 6 months of life. Children cannot hold their neck and do not reach their milestones of sitting and standing. Death occurs in up to 2 years of age due to respiratory failure unless child is given ventilatory support and intensive support at home.
• Type 2 children can sit but cannot stand independently or walk. They can breathe independently without ventilatory support. However, ventilatory support is needed during severe respiratory infections.
• Type 3 children attain sitting and walking milestones but thereafter lose strength in leg muscles and may lose ability to walk.
• Type 4 occurs late in life where adults slowly lose the ability to walk independently.

SMA is a genetic disease and is inherited from both mother and father who are carriers of the defective gene. If only one parent is a carrier then SMA will not occur in the child. The defective gene, the SMN 1 gene, has a missing segment (EXON 7) that disables its ability to produce full length SMN protein. This protein is essential for nerve and muscle function and in its absence the nerves and muscles don’t work properly. Another gene called the SMN 2 gene, which is like the SMN 1 gene, then takes over the work of producing the SMN protein. Unfortunately, it produces a shorter protein that is inefficient. Patients who have more copies of SMN 2 genes are better able to cope with the disease, whereas those with fewer copies face greater problems.

Inheritance of SMA. Both parents are carriers of the defective gene, that is they carry one defective gene. The affected child has both defective genes. The unaffected child is either a carrier or has both normal genes.

A GENETIC TEST determines the deletion of EXON 7 from Chromosome 5q of the patent’s genome, which confirms the diagnosis of SMA. Previously, various other tests like Electromyography (EMG) was also done but is now unnecessary. Another important test is the MLPA TEST FOR SMN 2 COPIES. This is also a genetic test that determines the number of copies of the SMN 2 gene. It is important for the eligibility of certain treatments like SPINRAZA.

Most of the leading hospitals of the country that have a Genetics Department will be providing tests to diagnose SMA and determine the number of SMN 2 copies. Below is a list of centers and private labs which provide these tests:

• Department of Genetics, AIIMS New Delhi
• Department of Genetics, Sir Gangaram Hospital, New Delhi
• Department of Genetics and Pediatric Research, Maulana Azad Medical College, New Delhi
• Department of Genetics, PGI Lucknow
• GeneTech, Hyderabad
• Medgenome, Bangalore
• Dr. Lal Path Labs (only SMA test)

There are more labs and hospitals that provide these tests. Enquire from your peid

Most of the leading hospitals of the country that have a Genetics Department will be providing tests to diagnose SMA and determine the number of SMN 2 copies. Below is a list of centers and private labs which provide these tests:

In the last 5 year, exciting milestones in SMA research have been reached. Two drugs have been approved by the U.S. FDA (Food and Drug Administration) for treatment of SMA:

• Spinraza by Biogen Inc.: Spinraza was approved for treating SMA in 2016. This medicine increases the amount of full length, efficient SMN protein produced by SMN 2 gene, therefore improving muscle strength and slowing disease progression. It requires 3 to 4 doses every year, lifelong. As of now it is available in the US and few other countries like Australia, Canada, Europe, etc. Spinraza is exorbitantly priced at $750,000 for the first year and $375,000 every year subsequently, therefore, limiting its availability. Read more at www.spinraza.com.
• Zolgensma by Avexis (Novartis): This gene therapy garnered approval in the U.S. in 2019 for children 2 years and under. This therapy uses a virus (AAV9 virus capsid) to deliver and insert a working SMN gene into the cell nucleus of motor neurons. This functional SMN gene produces the efficient full-length SMN protein thus allowing motor nerves to work properly. Zolgensma is a one-time treatment only as once the gene is inserted it continues to produce the protein for the patient’s lifetime. However, its effectiveness in children older than 2 years has not yet been established and clinical trials are underway. Cost of this medicine is approx. $ 2 million and is currently only available in the U.S. Read more here www.zolgensma.com.
• Others: Some other promising drugs in clinical trials are:
  • Risdiplam by Roche Pharma: this medicine is a small-molecule chemical compound that enables the SMN 2 gene to produce the functional full-length SMN protein. It is currently under trial in Europe. Read more here www.treatsma.uk.
  • Reldesemtiv by Cytokinetics: this medicine is being developed particularly for types 2, 3 and 4, to increase the force of muscle contraction and therefore muscle strength. It is in clinical trials. Read more here www.cytokinetics.com.

Apart from these, there are many other drugs under research and not yet in trial phase. FSMA India will keep updating information. Together with SMA families, researchers and the government FSMA India aims to bring an affordable and effective treatment available to all SMA patients in India.