DMD - L6

Question 1

Topics?

Answer 1

muscular degeneration
treatment is complex
possible solutions
   gene repair or replacement
   upregulation of compensatory proteins
   blocking downstream effects

Question 2

What does absence of dystrophin do?

Answer 2

disassembly of DAPC
increased sarcolemma fragility
increased calcium entry, damage to fibres

Question 3

Why is treatment complex?

Answer 3

skeletal muscle most abundant tissue in body

local delivery vs system delivery

Question 4

Gene repair of replacement topics?

Answer 4

Cell replacement
   MTT
   Stem cell therapy
Gene replacement
Nonsense mutation suppression
Targeted exon skipping

Question 5

Describe MTT

Answer 5

-

Question 6

Describe stem cell therapy

Answer 6

-

Question 7

Describe gene replacement

Answer 7

-

Question 8

Describe nonsense mutation suppression

Answer 8

(Ataluren trial)

Question 9

Describe targeted exon skipping

Answer 9

-

Question 10

Upregulation of compensatory proteins?

Answer 10

Utrophin 6q24

Question 11

Blocking downstream effects?

Answer 11

block abnormal Ca2+ influx
fibrosis: anti-fibrotics
immune: steroids, TNF-α antagonists, TGF-β antagonists
increase NO: arginine-like drugs
increase muscle energy: creatine/CoQ10
increase muscle regeneration: MYO-029, IGF, glutamine