Spinal Muscular Atrophy (SMA) is a rare, genetically inherited neuromuscular condition. It causes progressive weakness and wasting of the muscles leading to loss of movement. This in turn affects crawling and walking ability, movements of the limbs, breathing, and swallowing.

There are different types of SMA namely Type 1, 2, 3, or 4, and these represent the age of onset of symptoms and the extent of muscle weakness and motor milestones one would be expected to achieve. To understand it in simple terms, SMA is a ‘Spectrum’ (groups) with varying degrees of severity. The different types of SMA are diagnosed based on an individual’s ability to sit, stand, and walk; and knowing this helps make decisions regarding care and management. At times, SMA individuals are classified as ‘non-sitters’, ‘sitters’ and ‘walkers’. The severe and early form, namely SMA 1, is represented as ‘non-sitters’.

We know that SMA is a genetic condition. This implies that there is a fault in a specific gene called SMN1 in the individual. We have several thousand genes within us that make us who we are. Each gene has two copies, one copy from each parent. Most people therefore have two normal copies of the SMN1 gene as well. People with SMA have two faulty copies of the SMN1 gene. This means they are unable to produce enough SMN protein to have a healthy and functioning motor neuron (a type of nerve cell) in the spinal cord. The SMN protein is critical to the health and survival of the nerve cells in the spinal cord responsible for muscle contraction (motor neuron).

Motor neurons in the spinal cord (anterior horn cells) are structures responsible for transmitting the signal from the brain and spinal cord to the muscles. Therefore, in SMA, there is a progressive loss of these motor neurons leading to progressive muscle weakness.

The faulty genes are passed on in an Autosomal recessive fashion. This means each parent has one faulty gene and therefore they are called carriers and do not suffer from the condition. However, when both parents pass on this faulty gene to their child, he/she ends up getting two faulty copies (Homozygous), leading to them acquiring the condition. For these parents, the chance of having another child with SMA remains at 25% with every pregnancy.

So overall, there is only a one in 4 chance that the child will be diseased and a 3 out of 4 chance that the child will have a normal life.

SMA 1 is the most severe form of SMA and a child’s muscle weakness and milestone delay begins between 0 to 6 months. These children are unable to sit without support. They often have feeding and breathing difficulties due to their weak muscles. Most of these children, prior to current supportive treatments for breathing, were expected to live for less than two years. However, over the last 2 decades, since newer proactive managements were introduced like breathing support and feeding support, children have been living longer albeit with a compromised quality of life.

Until recently, there was no cure or disease-modifying treatment for SMA but over the last decade medical science and genetic therapeutics have made great strides in this field. We know that due to mutation in the SMN1 gene, the patient is not able to produce SMN protein. However, there is another gene called SMN2 which also makes SMN protein but at a greatly reduced efficiency, therefore producing a lower level of the protein. This SMN2 has provided an attractive target for developing SMA therapeutics and the majority of current research is focused on increasing SMN2 protein production from this gene.

Over the last decade, several approaches aimed at increasing production of the SMN protein have been developed.

Nusinersen (SPINRAZA) has been approved by the FDA (Federal Drug Authority) for use in all types of SMA since 2016. It is given intrathecally (by injecting into the fluid around the spine). This drug contains certain genetic material that binds to RNA (ribonucleic acid), so that the error in the SMN2 gene can be fixed and it starts producing more SMN protein. Starting treatment early shows better results.

More recently, AVXS-101 (Zolgensma) has been approved for patients less than 2 years. It is a form of gene therapy where the virus vector (carrier of the normal gene) delivers a fully functional copy of the human SMN gene into the target motor neuron cells (nerve cells in the spinal cord). It is an injection given one time to improve the motor ability of these children. However, the cost of this treatment is believed to be the highest ever set for a one-time treatment for any condition. Other novel drug treatments are also in the pipeline and these will help expand the options available for treatment.

Clearly, at the current price, this treatment would be out of reach for most families without the approval of insurance companies or other support.

We inadvertently blame the manufacturers for these high prices and the cost of life-saving therapies, but we must also remember that we need to ensure that medical researchers have the funds they need to carry out their research and deliver miracle cures like Zolgensma. If those prices were significantly capped, it would effectively halt medical innovation and thus abort the development of the next miracle cure. Having said that, we are hoping that with new treatment options in the pipeline, the cost of these life-saving and life-changing gene therapies will come down, thus enabling most, if not all, children with this devastating disease to benefit from this miracle of science.