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Nusinersen Treatment in Later Onset SMA - Results of the CHERISH Trial

28 March 2018

Read the following research article from our Clinical Care Research Correspondent, Dr Alex Murphy:


In February 2018, the prestigious New England Journal of Medicine published the results of the Nusinersen trial known as the ‘CHERISH trial’. This was a study that looked at the effects of giving Nusinersen to 126 children with later onset SMA1. The study had positive findings, and provides more evidence to support Nusinersen use in treatment of a later onset Type of SMA (i.e. Type 2). This article summarises the study methodology, results, and what this may mean for the SMA community.


Nusinersen is a medication that has beneficial effects in terms of developmental milestones and life span, when investigated in clinical trials with SMA Type 1 patients2.

SMA is caused by a problem within the SMN1 gene, which leads to reduced production of the protein called ‘Survival Motor Neuron’ (SMN). The SMN protein is important in making sure that the motor neurons, which are the nerve cells that connect the brain and spinal cord to muscles to allow conscious muscle contraction, are healthy. There is a second, “backup” gene (SMN2), which can produce this protein; however, SMN2 produces less SMN protein than SMN1.  Nusinersen works by modifying the SMN2 gene to increase production of the SMN protein. Nusinersen is given via a needle into the spine (medication given this way is called 'intrathecal'). 

Eugenio Mercuri and colleagues conducted the largest trial so far of Nusinersen in SMA Type 2, held across 24 different hospitals in ten countries. Children who were recruited had to have achieved sitting independently, but never have walked unaided (i.e. SMA Type 2). Participants had to have reasonable ability to move, and were assessed using a physiotherapy assessment tool (Hammersmith Functional motor scale-expanded)3. Participants couldn’t take part if they needed help with breathing, had significant curvature of the spine, or were fed via a tube (known as percutaneous endoscopic gastrostomy, or PEG).

In total, 126 children took part. Participants were given four intrathecal doses of Nusinersen (on days 1, 29, 85 and 274). Patients in the placebo group received a sham procedure without Nusinersen. In order to ensure that as few people as possible involved in the trial knew who was receiving the actual medication, participants were sedated when they were taken for the procedure. If the participant was having the sham procedure, a small cut was made as if they had undergone the actual procedure.

The main result that Mercuri and colleagues were interested in was a more than three point change in the physiotherapy assessment tool (which is out of a possible 66 points). Children had these assessments once every three months for 15 months. They were also interested in the percentage of children who improved from their first assessment, whether they improved on a physiotherapy assessment of their upper limb abilities, whether they achieved new developmental milestones, and whether there were any side effects of the drug.


Of the 126 children enrolled, 84 were given the treatment with the rest undergoing the sham procedure. As often happens in clinical trials, there was a check on results when the trial had been running for a while. The results were found to be sufficiently positive to stop the trial early, so that all of the participants could receive the drug. Therefore, about 80% of participants who took part had the 15 months assessment as planned.

The main result was change in physiotherapy score at the end of the trial, compared to before treatment. A difference in this score is said to be “clinically significant” (broadly meaning that the individuals would be expected to notice a difference themselves), if it is a difference of more than 3 points. The group receiving Nusinersen had an increase in the physiotherapy assessment tool score from before treatment (i.e. overall, their score increased after treatment). Those undergoing the sham procedure had a decrease in their score from baseline. Overall, in terms of how much the physiotherapy score had changed from before treatment in the two groups, there was an average difference of 5.9 points, which is a significant result. They also reported that the greater effect was seen in children who received the medication at an earlier age or closer to when the symptoms began.

For the other items the study looked at (the number of children achieving at least one new developmental milestone), although more children (20%) achieved this in the group treated with Nusinersen, according to statistical tests, this was not found to be significantly higher (compared to 6% in the group not receiving medication). Participants were also shown to improve in their upper limb abilities when assessed, but this was not significant.

Safety of the medication was assessed at each visit, with similar numbers of reported problems (termed ‘adverse events’) reported by both groups. No child stopped treatment due to safety concerns around the medication. This indicates that Nusinersen continues to be safe and well tolerated by patients.


This study provides additional support for Nusinersen as a treatment of SMA. In the past, Nusinersen has been trialled with individuals with SMA Type 14; in this CHERISH trial, it was given to a group of children with SMA Type 2. Mercuri and colleagues provided more evidence that Nusinersen was relatively safe and that the process of administering it into the spinal cord fluid is well tolerated in children.

The only real criticism of the study is that the group of participants involved was not very similar to a lot of the children in the wider world living with SMA, and may not have included those with more severe symptoms. This is perhaps demonstrated by the fact that Mercuri and colleagues didn’t include those with scoliosis, breathing issues, or those being fed via a tube. We therefore don’t know if the same significant effects would be seen in such individuals. In spite of this, this study demonstrated clearly that Nusinersen has beneficial effects in terms of muscle function when given to children with SMA Type 2, and the results also importantly suggested that earlier treatment may lead to greater benefit.

For the SMA community, this is an important study, and provides more evidence for the licencing and commissioning bodies (i.e. NICE) in their consideration over whether to make Nusinersen available on the NHS, and to whom.  



1.  Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, et al. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. New England Journal of Medicine. 2018;378(7):625-35.

2. Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017-26.

3.  O’Hagen JM, Glanzman AM, McDermott MP, Ryan PA, Flickinger J, Quigley J, et al. An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients. Neuromuscular Disorders. 2007;17(9):693-7.

4. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. New England Journal of Medicine. 2017;377(18):1723-32.