Parental trials in CR

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Parental trials in CR

• Ing. Miroslav Stuchlik
• Parent Project Czech Republic

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Parent Project

• Founded 2001
• Registry 2004
• Protandim 2007
• Haelan 2008
• UDCA ?

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Registry

• Part of Treat-NMD
• 202 patients from Czech and Slovak Republic
• http//dystrofie.registry.cz/

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Protandim

• Trial construction
• 17 boys 15 DMD, 1 BMD, 1 intermediate form
• Dosage ½ pill below 32kg, 1 pill above 32kg
• Duration 90 days
• Evaluated
• Parental observation
• CK, ALT, AST, LD
• Spirometry
• Osteopontin

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Protandim

• Parental observation
• Walking (endurance)
• evaluated only at ambulant
• improvement in 4 from 6
• No improvement 1 BMD, 1 another healthy issue
• Stairs (force)
• improvement in 4 from 6
• Later onset then in walking

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Protandim

• Parental observation
• Hands strength
• Improvement 5x all wheelchair bounded
• Again able drink without help
• Energy
• Improvement 13x

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Protandim

• Parental observation
• Learning, speaking
• Improvement 8x
• Speaking, memory, singing, better results at
  school
• Inflammation
• Improvement 9x
• Always only slight improvement

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Protandim

• Parental observation
• Better swimming
• Better sleeping
• Reduced pain in calves
• Not any improvement observed at BMD boy

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Protandim

• CK
• E strong bronchitis at the end of trial
• A, K, O still ambulant

Patient Before After Difference Diff. in
A 295 331 36.00 12.20
B 104.2 27.1 -77.10 -73.99
C 54.99 42.16 -12.83 -23.33
D 92.63 65.88 -26.75 -28.88
E 42.58 85 42.42 99.62
F 57.56 26,7  -57.56 -53.61
G 198 162 -36.00 -18.18
H 92.63 65.87 -26.76 -28.89
I 23.16 18.85 -4.31 -18.61
J 197.43 177 -20.43 -10.35
K 114.42 115.94 1.52 1.33
L 53.71 25.93 -27.78 -51.72
M 40.92 31.64 -9.28 -22.68
N 62.41 41.56 -20.85 -33.41
O 217 232 15.00 6.91
P  -  -    
Q 46.86 45.63 -1.23 -2.62
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Protandim
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Protandim
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Protandim
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Protandim
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Protandim

• Spirometry
• Only at some wheelchair bounded boys
• Results controversial
• Probably too difficult for boys with DMD

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Protandim

• Osteopontin (OPN,SPP1,Eta-1)
• Multifunctional protein, plays role in
• Mineralisation of tissues
• Regulation of inflammation
• Vascular diseases
• Imunne system
• Healing process
• Most upregulated gene and protein in mdx mice
• Contributing factor in the clinical progression
  of DMD
• Overexpression of Nrf2 significantly decreases
  mRNA expression of OPN
• Protandim activates Nrf2 and consequently ARE

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Protandim

• Overexpression leads to OPN polymerisation
• Polymerized OPN is supposed to have
  pathophysiological function

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Protandim
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Haelan 951

• Trial construction
• 18 boys
• Dosage
• 6 weeks 120ml/day
• 8 weeks 60ml/day
• Evaluated
• Parental observation
• CK, ALT, AST, LD, TNF-a
• Results recieved only from 9 boys

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Haelan 951

• Parental observation
• Walking (endurance)
• No improvement reported
• Stairs (force)
• No improvement
• Hands strength
• No improvement
• 1x decline

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Haelan 951

• Parental observation
• Energy
• Improvement 4x
• Learning, speaking
• Better concentration 2x
• Inflammation
• No improvement

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Haelan 951

• Parental observation
• Improved immunity
• Faster regeneration after illnesses
• Better sleeping
• Better respiration

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Haelan 951
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Haelan 951
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Haelan 951
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Haelan 951
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Haelan 951
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Ursodeoxycholic acid (UDCA)

• Non-corticoidal steroids
• Anti-inflammatory effect
• Upregulate utrophin
• Stimulate antioxidative system
• Amplifies action of Protandim at low
  concentration
• Used for other diagnosis, serious side effects
  not known

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Ursodeoxycholic acid (UDCA)
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Ursodeoxycholic acid (UDCA)
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