People with SMA do not have enough of a protein called ‘survival motor neuron’ (SMN) protein. This protein is essential for the nerve cells, known as motor neurons, that help control muscles. Motor neurons are found in the brain and spinal cord, and they make contact with muscles.

The SMN protein is made in our cells from two genes, SMN1 and SMN2. People who have SMA have:

• two ‘altered’ copies of the SMN1 gene. These are unable to produce enough SMN protein to have healthy lower motor neurons.
• a number of copies of the SMN2 gene. This is often called the back-up gene. It mostly produces a short SMN protein that does not work as well as a full-length protein.

Both treatments increase the amount of SMN protein found in cells throughout the body. They do this in different ways.

Spinraza

This is a small piece of genetic material (a synthetic antisense oligonucleotide). It targets the ‘back-up” SMN2 gene. It makes the gene produce more usable full-length SMN protein.

Risdiplam

This is a small molecule drug. It targets the ‘back-up’ SMN2 gene. It makes the gene produce more usable, full-length SMN protein.

If your clinician does not already have genetic test results that confirm you have 5q SMA they will:

• arrange for you to have a blood test. This will confirm if your SMA is caused by alterations in the SMN1 genes.  It will also show how many SMN2 gene copies you have.
• ask you when your symptoms started and how your condition has progressed.

This is so they can work out if your clinical diagnosis is Type 1,2, 3 or 4.

Spinraza

This is given by lumbar puncture. A needle is inserted through the skin into the space between the back bones of the spine (vertebrae) into the fluid that flows in and around the brain and spinal cord (cerebrospinal fluid -CSF). Doctors usually use a local anaesthetic such as ‘numbing cream’ when they do this. If a sedative or general anaesthetic is needed, the doctor will decide if this is safe for you or if a different treatment should be considered.

The total length of time the procedure  takes will vary. The injection itself takes between one and three minutes.

‘Loading doses’ are given to get the level of the drug to an effective concentration within the CSF. These are:

• On the first day of treatment, day 0
• Then around day 14, day 28 and day 63
• There should always be at least 14 days between doses.

Once the loading doses have all been delivered, there are then maintenance doses every 4 months to maintain the drug concentration level in the CSF.

Risdiplam

This is given as a liquid at home. It is taken daily after a meal, at approximately the same time each day. It is given by mouth (orally) or feeding tube, using the syringe that comes with it.  It is provided in a bottle in a box that must be kept in the fridge. It comes with instructions about how long it is safe to keep it out of a fridge.

In all cases you would have regular contact with your clinical team to check how you are reacting to your treatment.

Spinraza

This reaches the motor neurons and other cell types in the spinal cord. It may have limited ability to reach other parts of the body due to the ‘blood-brain’ barrier. It is not currently known how much SMN protein may be needed in other parts of the body.

Risdiplam

This reaches many different types of cell, tissue and organs in the body. This includes the brain, spinal cord, muscles and blood.

Your clinical team will discuss the possible risks and benefits of each treatment with you. To have Spinraza it must be technically possible and clinically safe for you to have an injection into your spine (an intrathecal injection).

You can read more on this topic if you follow the links at the top of this page. Each treatment also has a detailed Patient Information Leaflet:

There are no clinical trials or studies that directly compare the effect of these treatments.

When compared to no treatment, both treatments have led to clinically meaningful improvements in muscle function.

The long-term outcomes and the specific outcomes for any individual are uncertain.

Your clinical team will know about the clinical trials for each treatment. They will have ‘real world’ information that is being collected and discussed all the time.