People with SMA do not have enough of a protein called ‘survival motor neuron’ (SMN) protein. This protein is essential for the function of motor neurons. These are the nerve cells responsible for controlling muscles. Motor neurons are located in the brain and spinal cord. They form connections with muscles to enable movement.

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. When they are altered these genes are unable to produce enough SMN protein to maintain healthy lower motor neurons.
• a variable number of copies of the SMN2 gene. SMN2 is often called the back-up gene. It mostly produces a small amount of a short SMN protein that does not work as well as a full-length protein.

SMN protein is most important for motor development early in life. Increasing SMN protein later in life cannot restore lost motor skills.

Researchers know that adults lose their motor abilities more slowly over time. But the condition is still progressive. More SMN protein in adulthood may prevent a decline in motor skills and stabilize the condition.

Both treatments aim to increase the amount of stable SMN protein that SMN2 can provide.

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 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 and what is the allowed maximum temperature.

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

Both treatments reach the motor neurons to treat SMA.

Both treatments reach other types of cells. The extent of this, and any potential benefits, are unknown.

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.

Risdiplam

This reaches many different types of cells, tissues and organs in the body.

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.

Deciding whether to begin treatment and which treatment may be right for you is a personal and complex decision. Every person’s situation is different. What works best for one individual might not be the best choice for another. You might want to think about and discuss with your clinical team:

Your Health and Medical Needs.

How would you rate your current health and the progression of your SMA?

Your clinical team will assess your physical abilities, mobility, and overall health to help you understand how each treatment might benefit you.

Your Lifestyle, Convenience and Long -term commitment.

How would each treatment fit into your daily life?

Spinraza requires regular visits to a Regional Neuromuscular Centre (RNMC) and lumbar punctures. It involves an initial series of loading doses, followed by maintenance doses every four months.

Risdiplam is taken at home as a daily liquid. It needs to be kept in the fridge and taken daily. This requires consistency.

Risks and Side Effects.

Each treatment has its own risks and potential side effects.

Spinraza requires lumbar punctures. There are risks related to the lumbar puncture procedure. Sometimes it is too complex and challenging, for example for someone who has had a spinal fusion.  Your doctor will help determine it is possible and safe for you.

Risdiplam’s side effects might include symptoms such as diarrhoea or a rash. It is important to discuss these with your clinical team and to weigh up the risks and benefits for you.

Your Goals for Treatment.

What are your personal goals? Do you want to stabilise your condition or try to maintain current muscle function?

Both treatments aim to increase SMN protein and potentially stabilise motor function. However, it is important to set realistic expectations and understand that the long-term outcomes are still being studied.

Financial and Practical Considerations.

Although both treatments are funded by the NHS, there may be other practical considerations. For example:

You will need to be able to maintain the time and cost it will take to travel to hospital appointments for Spinraza. SMA UK’s FlexiGrant can help with travel costs for accessing treatment if needed.

You may need additional support at home for daily administration of Risdiplam.

Cerebrospinal fluid (CSF): The fluid that surrounds and protects the brain and spinal cord.

General anaesthetic: Medicine that puts you to sleep so you don’t feel pain during surgery or certain procedures.

Genetic test: A blood test to confirm the specific genes involved in SMA.

Intrathecal injection: Injection of medication directly into the space around the spinal cord.

Lumbar puncture > Involves a needle being inserted into your lower back, between the bones in your spine.

Motor neurons: Nerve cells that send signals from the brain or spinal cord to muscles, allowing movement.

Sedative: Medication that helps you relax or makes you sleepy during a medical procedure.

Small molecule drug: A type of medication made up of tiny particles that can easily enter cells and change how they work.

SMN1 gene: The main gene responsible for producing SMN protein, which helps keep motor neurons healthy.

SMN2 gene: A backup gene that makes a small amount of SMN protein, but not as effectively as SMN1.

SMN protein: A protein needed for motor neuron function, which controls muscle movement.

Synthetic antisense oligonucleotide: A small piece of lab-made genetic material designed to help a gene work better.