spinal muscular atrophy

Question 1

Genetics

Answer 1

autosomal recessive

disruption SMN1 gene

SMN2 gene compensates slightly although this gene itself has a splicing mutation of exon 7, meaning it produces mostly short and unstable protein

severity of disease based on how many copies of SMN2 they have

Question 2

axon pathology

Answer 2

axons aren’t formed as well as should be
synapses not maintained
muscles denervated

Question 3

non-neuromuscular pathology

Answer 3

cardiac arrhythmias & heart defects
digital and peripheral necrosis
vascular defects in skeletal muscle, spinal cord and retina
bone, pancreas, liver, kidney and spleen defective in SMA mouse models

Question 4

treatment: gene therapy

Answer 4

self-complimentary AAV
give healthy SMN1 gene back
ventral horn motor neurons take up healthy copy injected gene
need to do ASAP: doesn’t regrow motor neurons - stops further deterioration

Question 5

treatment: HDAC inhibitors

Answer 5

histone deacetylase inhibitors are non-specific regulators of transcription, careful design increases SMN2 promotor activity

control splicing