Zolgensma for spinal muscular atrophy

This resource is about the use of Zolgensma (onasemnogene abeparvovec) for spinal muscular atrophy. Your child has been offered treatment with Zolgensma for spinal muscular atrophy (SMA).

Zolgensma is only available at a few hospitals across the UK. Your child’s infusion centre is Sheffield Children’s Hospital. The Sheffield Children’s Hospital will:

• give the Zolgensma to your child by a single intravenous infusion (drip into your child’s veins)
• organise blood tests before and after treatment
• prescribe prednisolone (a steroid) for your child. This is an oral medicine that will need to be continued after Zolgensma. This may continue for a few months after Zolgensma depending on your child’s blood tests.

It is very important that your child’s overall care remains with their regional neuromuscular centre (RMNC) to make sure they receive the ongoing support they need.

What is SMA?

Spinal muscular atrophy (SMA) is caused by mistakes in both copies of the SNM1 gene (survival of motor neurone) which produces SMN protein.

There is a back-up gene SMN2 which only produces a small amount of stable SMN protein. Without enough SMN protein, the motor neurons do not work properly and may die resulting in muscle weakness. They are the cells which communicate messages from the spinal cord to muscle.

What is Zolgensma?

A healthy copy of the human SMN1 gene is put into a vector which delivers the SMN1 gene into the cells where it is needed.

The vector is an adeno-associated virus (AAV) 9. AAV9 is suitable to use in this way as it does not cause human disease. The virus has been altered so it cannot multiply. This means the virus can enter the nervous system and deliver the gene to motor neurons without causing infections.

Some people will have been exposed to AAV9 naturally and will have immunity to the virus so this treatment cannot be given. For this reason, checking immunity to AAV9 is needed before deciding on treatment.

The treatment involves injection of at least hundred trillion copies of the AAV9 vector with the SMN1 gene by intravenous infusion.

What are the possible side effects?

The main side effect of Zolgensma is inflammation in the body. The most common problems are:

• fever and being sick after the infusion which is usually temporary.
• a reduction in the number of platelets in your child’s blood. Platelets are small particles in the blood which help with clotting (stopping bleeding). If a reduction in platelet number happens it is usually in the first week after infusion and usually self-corrects and does not need any treatment.
• upset in liver function which does not usually cause any symptoms but is detected on blood tests.
• a rise in blood level of troponins. This is a test which could indicate heart damage but no children treated with Zolgensma in clinical trials experienced problems with their heart functions.
• very rarely a more serious condition thrombotic microangiopathy (TMA) affecting the kidneys has been reported.

What can be done about side effects?

Fever will be managed with paracetamol.

Being sick will be managed by encouraging drinking fluids or sometimes giving intravenous fluids.

Liver inflammation is reduced by starting steroid treatment (prednisolone) 24 hours before the infusion and continuing for at least 2 months. The duration of steroid treatment and the dose will depend on the results of blood tests and communicated to you by the infusion centre team after monitoring blood tests.

Frequent blood tests will be needed for safety reasons to check your child’s platelets, liver and troponin. These will be weekly for the 3 months. Clinical reviews will be weekly for the first month and then every 2 weeks for the 2nd and 3rd months after the infusion.

Blood tests and clinical reviews may be more frequent or continued for longer depending on the results.

If the investigations are abnormal you might be asked to bring your child for review or advised a change in steroid dose.

Please let us know about any problems or side effects your child might have, including anything that is not mentioned in this resource.

What will happen if my child has this treatment?

Your local neuromuscular centre will refer your baby to the infusion centre if:

• your baby is less than 7 months old and not on any SMA treatment currently, or
• your baby is more than 7 months and on treatment already

The team at your local neuromuscular centre will liaise with the team at the infusion centre.

You will be contacted by phone by the infusion centre team with an appointment for an initial meeting. At this meeting the doctors will discuss the treatment benefits and risks with you. You will need to sign your consent.

Your child will be examined and weighed and may need to have repeat blood tests.

What happens next?

A date for the infusion will then be arranged.

Your child will be admitted on a day-unit called OPAT. This means that they attend in the day only for 3 days.

Day 1

On day 1 they will have:

• observations
• bloods test
• urine test
• medical assessments
• physiotherapy assessments
• speech and language therapy assessments
• prednisolone treatment

Day 2

On day 2, Zolgensma infusion will be given to your child over 1 hour.

2 cannulae (a small plastic tube put into your child’s veins) will be inserted in case one does not work during the infusion and your child will be observed throughout this infusion.

Day 3

On day 3 your child will be have blood and urine tests done and observations. If everything is fine, they may be discharged but may need to remain in hospital if there are any complications.

Sometimes, children may be admitted to the ward instead of OPAT.

After the infusion

After the infusion, blood tests will be arranged. This may be at the infusion centre, your local neuromuscular centre, or local paediatric centre. The results of these blood tests will be monitored by infusion centre team who will communicate with you if any actions such as clinical review or change in steroid dose are needed.

Before your child is discharged, the infusion centre team will have a meeting with the local neuromuscular centre team to discuss the details of your child’s treatment and make plans for the safety monitoring bloods. On discharge a document with these details and other important information will be given to you and sent to relevant health professionals.

If your child is unwell after Zolgensma and need a review with health professionals, please bring this resource with you so they can help you better and know what to look out for.