SMA
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Onset |
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SMA1 |
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SMA2 |
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SMA3 |
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SMA4 |
>10years |
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• SMN gene
o SMN 1 – stable
o SMN 2 – unstable, does not transcribe exon 7 – protein breakdown
o Disease severity is roughly proportional to the number of SMN2 gene copies
• Cardiac
• GIT
• Bone
• Neural/muscle
• Nusinersen
o Antisense oligonucleotide that modifies splicing of SMN2
o Increases the synthesis of transcipts that contain exon 7 (i.e. normal)
o ENDEAR trial
- 122 patients with clinically evident SMA 1
- Significant improvements in motor milestones
- Reduced mortality
o NUTURE
- Pre-symptomatic patients with gene defect for SMA 1
- 18 patients
• AVXS101
o Adenovirus designed to deliver SMN1 transgene
o Single IV infusion
o 12 patients
o