Nusinersen belongs to a group of medicines known as antisense oligonucleotides. It is only used to treat 5q spinal muscular atrophy (5q SMA).

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 lack the SMN1 gene but have the SMN2 gene. This mostly produces a short SMN protein that does not work as well as a full-length protein.

Nusinersen is a small piece of man-made genetic material (a synthetic antisense oligonucleotide). It targets the SMN2 gene and enables it to produce more functional, full-length SMN protein.

Nusinersen is manufactured by the pharmaceutical company Biogen under the trademark SPINRAZA™.

More detail on how nusinersen works in SMA >

Our nervous system is protected by a border called the ‘blood-brain barrier’. Nusinersen cannot cross this border so it has to be injected directly into the  cerebrospinal fluid (CSF). This fluid flows in and around the hollow spaces of the brain and spinal cord, and between two of the meninges (the thin layers of tissue that cover and protect the brain and spinal cord). Nusinersen is injected directly into the CSF via an injection into the spinal cord.

Once injected, nusinersen reaches the motor neurons and other cell types in the spinal cord. It may have limited ability to reach other parts of the body. We currently do not know how much SMN protein may be needed in other parts of the body.

Nusinersen is delivered directly into the cerebrospinal fluid (CSF).

Doctors access the CSF using a lumbar puncture.

A needle is inserted through the skin into the space between the back bones (vertebrae) of the spine. Doctors may need to use imaging methods via X ray or CT scan to find the best place for the insertion. They usually use a local anaesthetic such as ‘numbing cream’.

During the procedure older children or adults can be offered Entonox (gas and air). Some need a sedative and occasionally a general anaesthetic may be considered necessary. The treatment centre will have an individual discussion with you about what the best option would be for you or your child.

A small amount of CSF is collected and then nusinersen is injected over one to three minutes.

All healthcare professionals who perform this procedure receive specific training to perform intrathecal injections

The treatment can only be delivered by lumbar puncture. This procedure needs to take place within one of the Regional Neuromuscular Treatment Centres.

Any drug, including ones that are commonly prescribed or sold over the counter, may cause possible side effects. Side effects of medications are reported and recorded during their clinical trials. They are also picked up through the ongoing systems that are in place to monitor medications and their use in the ‘real world’.

All possible side effects are listed in the Patient Information Leaflet that is given with any medication. They are grouped as:

• very common
• common
• uncommon
• rare.

Side effects related to the lumbar puncture may occur while nusinersen is being given or afterwards. The majority of these side effects are reported within 72 hours of the procedure.

Very common: may affect more than 1 in 10 people:

• Back pain
• Headache
• Vomiting

These and any rare or very rare side effects are listed in Biogen’s Patient Information Leaflet which covers other questions as well (see Q 13 below).

Read about the risks of lumbar puncture in general >

The total length of time the treatment takes depends on many factors. The procedure can be very quick or can take a long time. The treatment centre is best placed to advise how long it may take to treat you or your child.

Injections are given as follows:

A series of first doses called ‘loading doses’ are administered to get the level of the drug to an effective concentration within the CSF.

These loading doses take place:

• 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. These are once every 4 months to maintain the drug concentration level in the CSF.

Recovery time is different for each person.

If the procedure is very straight forward and has been done many times before, a short stay in hospital may be all that is needed.

If it is the first treatment or complicated, a longer hospital stay may be needed after. This applies if sedation is used too.

Treatment needs to continue unless the treating clinician and you or you and your child agree that it should stop. If your treatment is covered by the England Managed Access Agreement, please see: When Might Treatment Stop?

The time it takes to see a response from treatment varies between people. It depends on many different factors. Some people may see improvements and respond within a few months after loading doses. Families with children have sometimes reported responses before they appear on motor assessment scores. Others take longer, up to a year.

A rule of thumb is that the more severe the muscle weakness, or the longer a person has had SMA, the longer it may take to see benefits from treatment.

If a dose is missed, the next dose should be given as soon as possible. The timing for this will depend where you or your child are within the treatment schedule.

If you have any questions or concerns about a safe time between doses or a dose being late, talk to your or your child’s treating clinician.

If you are in receipt of benefits and/or on a low income, you can get help with travel costs through the Healthcare Costs Travel Scheme. You should ask your treatment centre about any possible accommodation options.

You can also ask your clinical team – in particular the Neuromuscular Care Advisor or Nurse Liaison if there are any other possible sources of financial help.

The Family Guide to the Standards of Care describe which assessments and interventions children and adults should expect to have from any neuromuscular centre anywhere. They were agreed in November 2017. This was before drug treatments like nusinersen became widely available. A 3 – year project SMA Care UK is now underway to update these standards.  Your clinical team will be up to date with any changes to recommendations.

Many hospitals can provide emotional support services. If this service does not exist at your hospital, you should consider contacting your GP for local emotional support services. The SMA patient charities are also a good source of support.

You will find the answer to many of your questions in Biogen’s Patient Information Leaflet.You can discuss any further questions you may have with your or your child’s clinician. The leaflet covers:

1. What Spinraza is and what it is used for

2. What you need to know before you or your child take Spinraza

3. How to take Spinraza

4. Possible side effects

5. How to store Spinraza

6. Contents of the pack and other information

There are now three drugs funded by the NHS for people who have SMA. Until 2018 there were none. Different eligibility criteria apply to each one.

There have been no studies to date that directly compare the treatments. You will be able to discuss treatment options with your clinical team. Together you will be able to discuss the risks and benefits of any of the treatments that are potentially possible. You will be able to make an informed decision as to which one is best for you or your child.