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For our lower motor neurons to function and remain healthy, our cells need to produce the survival motor neuron (SMN) protein. The ability to do this is mainly controlled by the survival motor neuron 1 (SMN1) gene.

The SMN2 gene also contributes to the production of SMN protein, though it only makes approximately 10% of that produced by SMN1. For this reason, SMA is caused only by mutations in the SMN1 gene and not SMN2, and also why SMN2 is often called the SMN ‘back-up’ gene.

Anyone who has SMA has at least one copy of the SMN2 gene. Individuals can have multiple copies of SMN2, and, in general, it seems that those with more copies have a less severe form of SMA.

Most of the SMN protein made by SMN2 (about 90%) is missing an important piece called exon 7. The remaining 10% of the protein produced by SMN2 includes exon 7 and is the same as that made by SMN1. A number of treatment strategies that target SMN2 to make more functional SMN protein are being explored; they aim to do this in one of three main ways:

  • Correct SMN2 splicing, allowing SMN2 to more efficiently produce functional SMN protein:



  • Increase the protein production from SMN2 leading to more functional SMN protein.


  • Stabilise the functional SMN protein made by SMN2 and therefore make it last longer.

Nusinersen is not a classical gene therapy because the treatment does not directly modify a person’s genes. However, it is sometimes regarded as a ‘gene therapy’ as it impacts how the messenger RNA from the SMN2 gene is used to make SMN protein.

Antisense oligonucleotide drugs are small snippets of synthetic genetic material that bind ribonucleic acid (RNA). They are often described as molecular patches because they can be specifically designed to target and affect how a particular gene is read. ASOs have great potential for SMA, because they can accurately target the SMN2 gene to essentially convert it into the SMN1 gene, i.e. they are small molecules “patching-up” SMN2 to act more like SMN1. They do this by binding to the RNA template made by SMN2 and enhancing the inclusion of Exon 7 into the SMN protein. (See the above link for a more detailed explanation).

Between 2011 – 2021 there have been phenomenal developments using this treatment approach – notably with nusinersen. Further updates about clinical trials and treatments using nusinersen are tracked in these pages and in any relevant combined therapy investigation trials, here. New trials of new drugs using this approach will still be tracked here:


18th March: Biogen develops BIIB115, a potential new treatment for SMA


17th September: Biogen announced ASCEND Trial to evaluate higher doses of nusinersen for those who have had the maximum dose of 5 mg of risdiplam before joining the study and who are willing and able to change their treatment regimen to a higher dose of nusinersen.

22nd April: Biogen presented new data from its DEVOTE study of Spinraza.

11th January: First patient enrolled for RESPOND study of Spinraza


21st July: Biogen announces Phase 4 RESPOND study of Spinraza in patients treated with Zolgensma.

3rd July: Our Scientific Research Correspondent Dr James Sleigh reported on further small studies that support the use of nusinersen for SMA treatment in adults.

12th June: Positive results published for the NURTURE study of nusinersen.

27th March: Our Scientific Research Correspondent Dr James Sleigh reported on Dr. Hagenacker and team’s study which showed nusinersen is safe and effective for SMA treatment in adults.


28th June – 1st July: NURTURE study presented at CURE SMA Conference

24th October: Two new studies show positive effects of nusinersen in later-onset SMA.

10th May: Data from NURTURE study shows pre-symptomatic infants treated with Spinraza achieve motor milestones more consistent with typical development

19th May: Results of studies of later onset SMA suggest long-term benefits of Spinraza


15th December: Summary and comparison of results to date for nusinersen and gene therapy published – read more.

15th November: Updates on the trials presented at the 22nd International Annual Congress of the World Muscle Society (WMS) October 3rd-7th 2017: Poster 1 – CHERISH; Poster 2 – EMBRACE; Poster 3 – ENDEAR

25th April: Updates on the CHERISH and NURTURE clinical trials presented at the annual American Academy of Neurology meeting being held in Boston, USA (April 22nd-28th)

11th January: Novel antisense therapy removes the brakes on SMN protein production.


23rd December: The U.S. Food and Drug Administration approved Spinraza (nusinersen) – the first drug approved to treat children and adults with spinal muscular atrophy (SMA)

15th December:

31st October: FDA accepts nusinersen for priority review

22nd September: Matthew Wood’s laboratory shows molecular ‘homing devices’ drastically improve SMA Therapy.

11th May: Ionis Pharmaceuticals released updated information on EMBRACE.

31st January: Biogen and Ionis Pharmaceuticals provide updates on trials with nusinersen – also now known as Ionis-SMNRx and ASO-10-27 and previously known as ISIS-SMNRx – ENDEAR; CHERISH; NURTURE; EMBRACE; SHINE.


23rd October: ISIS Pharmaceuticals initiates SHINEstudy

16th June: ISIS Pharmaceuticals announces update on its ongoing Phase 11 study showing that ISIS-SMNRx continues to be well tolerated and appears to be having a positive effect on the disease progression.


14th October: at the 19th International World Muscle Society Congress in Berlin, ISIS Pharmaceuticals released detailed positive results from their Phase II clinical trials with infants with SMA Type 1 and other children with SMA type II

8th August: ISIS Pharmaceuticals announces beginning of Phase 111 study


7th November: Isis Pharmaceuticals started a Phase Ib/IIa clinical trial of ISIS-SMNRx in 24 children with SMA (ages 2-15)

5th January: Biogen Idec entered a global agreement with ISIS Pharmaceuticals to develop and commercialise their compound ISIS-SMNRx.


9th December: ISIS Pharmaceuticals had recently begun a Phase I clinical trial of their antisense oligonucleotide drug ISIS-SMNRx in medically stable SMA patients between 2-14 years of age.

The US Food and Drug Administration (FDA) had granted Orphan Drug Status with Fast Track Status to ISIS-SMNRx for the treatment of SMA patients.

Injection of a similar drug was safe and well tolerated by patients with a type of adult-onset motor neuron disease called amyotrophic lateral sclerosis (ALS), which is positive for the ISIS-SMNRx Phase I trial.

In the reported study, ISIS-SMNRx administration in SMA mice caused an increase in SMN protein levels, which in turn led to increased survival, reduced motor neuron loss and behavioural improvements. Furthermore, in a separate study, intrathecal administration of ISIS-SMNRx into cynomolgus monkeys resulted in putative therapeutic drug levels throughput the spinal cord (a key area of the body in the disease).

ASOs were used in mice to show that it is likely that SMN protein levels will need to be restored throughout the body, and not just the nervous system, in order to have the best chances of successfully treating the disease in patients.