Dystrophin

1
??????? ??????? ?????? ??????????????

• ?"? ???? ???
• ????? ????????????? ??????
• ??"? ???

2
Dystrophin Positive
Dystrophin Negative
3
DMD Muscle Biopsy
Normal
DMD
4
???????? ????????

• ???? ????? ????? ?????????? ??? ?????? ??????
  ????? ?????, ?? ?? ????? ?????? ????? ?????
  ??????
• ?????? ???? ???? ??? ???? ?????? ??? ?? ?????
  ???? ?????
• ??? ????? ?????? ???? ? SMA
• ????? ???? ?????? ?????? ????????????????
• ????? ??????

5
Steroid side effects obesity, hypertension,
growth retardation, behavior problems, bone
fragility
6
?????????

• Deflazacort - ??????? ????? ????? ???? ?????,
  ??? ???? ?????? ?? ?????
• ???????? ?????? ?????? ??? ????? ???? 10 ????
  ?????, ??? ??/ ??? ??, ??????? ??? ?????? ??????
  ?????.
• Oxandrolone ??????? ?????? (?????? ????????)
  ???? ??? ???? ?????? ???? ?????????

7
??????? ???????

• ??????? ???????? ?????????
• ????? ?????? ?????? ????? ??????? ?????????? ??
  ?????? ???? ????? ?????? ?????
• ?????? ?????? ???????? ????

8
Proposed pathophysiological cascade in DMD based
on gene expression profiling
Drugs with potential to interrupt the theorized
DMD
pathophysiologic
cascades
Drugs with potential to interrupt the theorized
DMD
pathophysiologic
cascades
Prednisone
Prednisone
11
11
1
3
5
7
9
CoQ10
Glutamine
IL
-
1 RA
Taurine
1
3
5
7
9
CoQ10
Glutamine
IL
-
1 RA
Taurine
Pyridoxine
Pyridoxine
12
carnitine
Nicotinic Acid
Creatine
Oxatomide
EDTA
Pentoxyfilline
Nicotinic Acid
Creatine
Oxatomide
EDTA
Pentoxyfylline
4
2
6
8
10
4
2
6
8
10
11
11
12

9
Animal models for DMD
XMD Cat
mdx mice
10
Golden Retriever Dog with DMD
11
?????? ?????????

• ?????? ???? ??????? ?????? ??? ?????? ??????
  ???????
• ????????? ????? ?????? ????? ????? ???? ????
  ??????? ????? ???? ?????
• ?????? ??? ????? ?? ??????????? ????? ????
  ?????? ?????
• ?????? ??????? ?????
• ???? ???? ???? ????? ???? ?????? ????? ?? ?????
  ?????? ???? ?? 3 ???? ?- 10 ?????? ??? ???????
• ?????? ?? ?????? ??? ?????? ?????

12
Albuterol

• Beta 2 agonist - ????? ?????? ??"?
• ????? ????? ???? ???? ????? ????? ?????? (FSHD)
• ????? ???? ???? ???? ???, ?? ???? ?? ????? ????
  ????? ??? ?????? ???? ?? ???? ????? ????

13
??????? ????????????????

• Cyclosporine ????? ???? ??? ??????
• ?????? Azthioprine ???? ??? ???? ????? ????
• ?????? ?????? ????? ???? ???? ?????? ???

14
Garamycin- Gentamycin

• ????? ?????????? ??? ??????? ???? ????? ?????
  ????? ?? ????? ?????
• suppression of stop codon
• ???? ??????? ??????? ???? ??? ???????? ???????
  (???????? ?????? ????? ????? ?????? ??????) ??
  ?????? ????

15
??????? ?????? Gene Therapy

• ???????? ??????? ??????
• ????? ?????
• ?????? ??????? ?????? ???
• ????? ????? ?? ????? ?????

16
???? ????? ????? ??????? ??????

• myoblast transfer ????? (?????) ???? ?????? ??
  ???? ?????. ????? ????? ?? ????? ??? ?????? ????
  ?? ?????? ????. ????? ???? ???????? ??????? ??
  ?????? ????
• ???????? ?????? ??? ?? ?????? ???? ????? ??
  ????? ????? ??? ( ??"? ????? ?????)
• ???????? ????? ???????? ????? ??? ????? ????
  ???????? ???? ?? ????? ?????????? ???? ?? ?????
  ????? ?????? ?????? ?????? ????
• Stem cells Therapy- ???????? ??????? ???? ?????
  ????? ?????? ???? ???? ???????? ?? ??? ??????
  ???? ????

17
????? ????? ??????? ?????? ???? ?? ????? ?? ?????
?

• ????? ????? ????? ??? ???? ????? ???? ?????
  ???? ?????? ?????, ???? ?????? (???? ?? ????)
• ???? ?????? ?? ?? ???? ??? ????????? ???? ????
  (?????? ????? ???? ????)
• ???? ?????? ???? ??? ???????
• ????? ???? ?? ???? ?????? ????? ??????? ?????? ??
  ???
• ??? ?????? ????? ???? ?? ????? ???? ??? ???? ????
  ??? ????
• ?? ?? ??? ???? ????????? ?????? ????? ?? ????

18
?? ???????? ???????? ?????? ???

• ????? ??????? (?????? ?? ?????) ???? ????? ??
  ???? ?????? ??? ????? ?????? ???? ???? ?????
  ????? ????? ??? ????, ????? ????? ???? ??????
  ??????? ??? ????? ???????
• ????? ??????? ????? ????? ?????? ?? ??????
  ???????? ?? ???? ?????? ?????

19
????? ?????? ???????? ??????? ??? ?????? ??????
?? ?????? ?????

• ??? ?????? ?????
• ????? ???? ????? ??? ????
• ??? ????? ??????????? ????? ???? ??????? ??
  ???? ????? ??, ?????? ????? ?????
• ???? ???? ????? ????? ?????? ???????
• ?????? ????? ?? ?????? ???? ??? ?????? ??????
• ????? ??????? ??????? ?? ???? ??????