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

People with SMA don’t 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, which mostly produces a short SMN protein that does not work as well as a full-length protein.

Nusinersen is a synthetic antisense oligonucleotide (a small piece of man-made genetic material) that 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 delivered directly into the cerebrospinal fluid (CSF) via an injection into the spinal cord. Upon injection, 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 vertebrae (back bones) of the spine. Doctors may need to use imaging methods via X ray or CT scan to locate the best place for the insertion. They usually use a local anaesthetic such as ‘numbing cream’. During the procedure older children / adults can be offered Entonox (gas and air), but 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 / 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 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’re 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.

For nusinersen, 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 will depend 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 / 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. 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 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 received multiple times previously, then a minimal time in hospital may be all that is needed. If it’s the first time that treatment has been given, or the procedure to deliver treatment is complicated, or if sedation is used, then a longer stay in hospital after the procedure may be necessary.

Treatment needs to continue unless the treating clinician and you / 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 therapy is variable between people and depends on many different factors. Some people may see improvements respond within a few months after loading doses and others take longer, up to a year. Families with children have sometimes reported responses before they appear on motor assessment scores. A rule of thumb is that the more severe the muscle weakness in a person or the longer they have lived with SMA, the longer it may take to show benefit from therapy.

If a dose is missed, the next dose should be administered as soon as possible. The timing for this will depend where you / your child are within the treatment schedule. If you have any questions or concerns about ensuring a safe time between doses or a dose being given later than planned, you should discuss these with your / your child’s treating clinician.

Though they’re not formal guidelines, the International Standards of Care for SMA describe which assessments and interventions families and adults should expect to find in any neuromuscular centre anywhere. They were agreed in November 2017 by a committee of international healthcare and patient experts. Follow the link to the Family Guide to the Standards of Care.

Many hospitals can provide emotional support services. If this service doesn’t 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 and will have an opportunity to discuss any further questions you may have with your 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 licenced 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 should discuss treatment options with your / your child’s clinical team in your specialist neuromuscular centre. Together you will be able to discuss risks and benefits of any of the treatments that are potentially possible and make an informed decision as to which one is best for you / your child.