It is a disease of motor neurons in the spinal cord, the lower motor neurons, resulting in progressive muscle weakness.

What is a motor neuron?

Neurons are the cells that make different parts of nervous system, like bricks for a building. Largest collection of neurons is in the brain, making its complicated circuitry. Some neurons act as nerves, like wires, taking messages towards or away from the brain. Sensory nerves take messages towards the brain, and motor nerves in opposite direction, from the brain to the muscles. Each nerve, a neuron, has a cell body with a central nucleus and surrounding cytoplasm. From that body comes out an extension, like a wire, sometimes delivering messages far away from its body.

Motor neurons are classified as of two types, upper motor and the lower motor neurons. Cell bodies of the upper motor neurons are in the brain, and of the lower in the spinal cord. The cell body and the nuclei of lower motor neurons reside in the spinal cord with an extension coming out in the form of short or long nerves. A material called myelin, like an insulation, covers this extension. Unlike a conventional wire that is uniformly coated with plastic, the myelin coating of nerves has gaps at regular intervals. These gaps are called nodes of Ranvier, which help to speed up the process of message transfer. Some motor nerves are more than a meter long, starting in the back and traveling down to our feet. 

 

What exactly is the reason for SMA?

It is caused by degeneration or dying of motor neuron cell bodies in the spinal cord. The underlying reason is a gene defect, somewhat different for each variety of SMA.

 

What are different types of SMA?

This subject is rapidly evolving as specific genetic defects are discovered. Traditionally, SMA is divided as follows:

SMA Type 0: Very severe muscle weakness right after birth, with life expectancy of less than a month.

SMA Type 1: Severe weakness starting in young age, less than 6 months, when a child is unable to sit. It is one of the most common genetic causes of death in children.

SMA Type 2: Appears little bit later, and a little less severe, when a child is able to sit but not able to walk.

SMA Type 3: Weakness appears in childhood but the child is able to walk.

SMA Type 4: Milder disease appearing in adulthood.

 

Is SMA a genetic disorder?

Yes, a genetic defect on chromosome 5 is the cause of different varieties of SMA. Its mode of inheritance is autosomal recessive. In this type of inheritance, one may have an abnormal gene without the disease (a carrier state). The person having the disease has abnormal genes on both chromosomes 5. A union of one parent as a carrier, and the normal other does not cause the disease. For the disease to appear in a child, both parents must have the abnormal gene. If both parents are carriers of the abnormal gene, the risk for the child is 1 in 4 (25%), and the risk is higher if one parent is a carrier and the other has the disease. Genetic basis of the disease is more complex than this outline, as patients may present with different severity of the disease (different phenotype), with somewhat similar gene defect (genotype).

 

How is SMA diagnosed?

Generally speaking it is diagnosed based upon its clinical features. More definitive or genetic testing is also utilized if available.

 

Is there a treatment for SMA?

Gene therapy has transformed treatment option for SMA. With no available treatment until a few years ago, now there are multiple options. Three gene-therapy based drugs are available for infants with SMA. They are as follows:

1. Nusinersen: It is given as series of injections in the spinal fluid. It helps to significantly improve muscle strength in infants. It can be tried in SMA2 but the response is not as significant as in younger age.
2. Onasemnogene abeparvovec-xioi: It is given as one intravenous infusion. It can help less than 2 years old infants with SMA.
3. Risdiplam: This is an oral medicine.

This is an active area of research and more treatment options are expected in near future. One of the problems with gene therapy is its cost. Cost of Nusinersen and Risdiplam is in hundreds of thousands of USD a year, and the cost of Onasemnogene injection is more than a million.

 

Where can I get more information about SMA?

American Academy of Neurology

Child Neurology Society