gene therapy

Question 1

What causes Duchene muscle dystrophy?

Answer 1

lack of dystrophin (important for mechanical anchoring of cells) due to exon skipping (exon 49 to 50 skipped –> premature stop codon)

Question 2

How does eteplirsen treat duchenne muscle dystrophy?

Answer 2

restores reading frame –> shortened, functional dystrophin produced

Question 3

How effective is nusinersen?

Answer 3

very effective in children: deadly events reduced by 50 %

adults: some respond to it, but it takes time

Question 4

How does SMN1 AAV9 gene replacement work? (Zolgensma)
And why does it only work shortly after birth?

Answer 4

only works in the first weeks after birth because then children develop antibodies against AAV but only one application needed
AAV transports gene into nucleus –> DNA polymerase transcribes dsDNA which is transcribed by RNA polymerase into mRNA which is then translated in the cytoplasm

Question 5

Name gene therapies to tgreat spinal muscle atrophy

Answer 5

• Nusinersen
• Zolgensma
• Risdiplam

Question 6

How does Risdiplam work?

Answer 6

it is a splicing enhancer that stabilizes exon7

Question 7

How can ALS be treated?

Answer 7

with tofersen

if patient has SOD1 mutation an intrathecal antisense oligonucleotide can be used to reduce SOD1 and Nfl