Presentation on theme: "SMA and Nusinersen (Spinraza) The Story So Far...."— Presentation transcript:
1 SMA and Nusinersen (Spinraza) The Story So Far.... Jennifer DunneNeuromuscular Clinical Nurse Specialist – RHC - Glasgow
2 Aims: Basic genetics of SMA The history of Nusinersen and how it works Clinical trialsThe development and delivery of Nusinersen in RHC – GlasgowPractical considerations as time goes onCase study – 1 year on from Nusinersen
3 What is SMA?SMA is a fault in the gene (SMN1) that codes for the Survival Motor Neurone (SMN)We have two copies of SMN1, one from each parent.The affected child is unable to make enough SMN protein as SMN1 is deleted or mutatedLeading to loss of functional motor skills.
4 SMA SMA is unique : second copy of the SMN gene, SMN2 Patients survive owing to the SMN2 gene.The more SMN2 copies the more SMN protein producedSMA TypeOnsetFeaturesLikely SMN2 copy numberPrenatalContractures, facial diplegia, respiratory failure1< 6 monthsPoor tone, weakness, mild contractures, tongue fasciculations26 - 18monthsLow tone, absent reflexes, may sit independently3-43Childhood, > 18 monthsAble to walk 25 metres, onset of falls ~ age 2-34Adult onsetWeakness with onset in adulthood4-8
5 Nusinersen and the SMN2 Gene Nusinersen is an Antisense Oligonucleotidesmall snippets of synthetic genetic material that bind to ribonucleic acid (RNA)
6 Basically NusinersenImproves expression of the SMN2 gene, converting it into SMN1 gene, thus increasing the level of SMN protein.
7 History of Nusinersen 2012 development began 2015 Biogen acquired exclusive license2016 Nusinersen met its primary end point2016 Biogen opened the Expanded Access Program – due to stop on Nov 20182018 (May) SMC approval of Nusinersen on the NHS for SMA 1 only – in Scotland2018 (Aug) NICE did not approve it as a treatment for SMA – in England
8 Clinical TrailsENDEAR Phase 3 – 2014 terminated early 2016 CHERISH Phase 3 – 2014 until 2017 (closed early) EMBRACE Phase 2 – 2015 until April 2019 NURTURE Phase 2 – 2015 until Jan 2022 SHINE Phase 3 – 2015 until 2022
9 Delivery of Nusinersen in RHC – Glasgow 2016 Biogen opened ‘Expanded Access Program’2 patients 1st injection 8th Jun ‘173rd patient 1st injection 7th Dec ‘174th patient (SMA2) 1st injection 3rd Mar ‘18 - via NHS fundingSMC approval May 2018 – now all funded by NHS
11 Practical Considerations LP procedure is becoming more difficultDevelopment of scoliosisThe site is developing scar tissueThe patients are getting older and more aware of what we are doingThey are getting stronger - wriggling
12 Practical Considerations We need to consider aesthetic procedure – midazolam unsuccessfulNeed a specific theatre list not just emergency listProtocol/Guidelines need developedImplications for adult patients are huge
13 SMA type 1 treated with Nusinersen are not SMA type 2 patients New Phenotype
14 Case Study – Sophia Diagnosed April 2017 aged 6 months 1 copy of SMN2 1st treatment on 8 June 2017 aged 8 monthsBaseline CHOP was 37After 6th injection 48 but more like 54No respiratory issuesNo feeding issuesDeveloping scoliosis – referred for lycra suitLeg length discrepancy