Parental trials in CR

1. Parental trials in CR Ing. Miroslav Stuchlik Parent Project Czech Republic

2. Parent Project • Founded 2001 • Registry 2004 • Protandim 2007 • Haelan 2008 • UDCA ?

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

4. 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

5. 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

6. Protandim Parental observation • Hands strength • Improvement 5x – all wheelchair bounded • “Again able drink without help” • Energy • Improvement 13x

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

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

9. Protandim • CK • E: strong bronchitis at the end of trial • A, K, O – still ambulant

10. Protandim

11. Protandim

12. Protandim

13. Protandim

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

15. 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

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

17. Protandim

18. Haelan 951 Trial construction • 18 boys • Dosage: • 6 weeks: 120ml/day • 8 weeks: 60ml/day • Evaluated • Parental observation • CK, ALT, AST, LD, TNF-α • Results recieved only from 9 boys

19. Haelan 951 Parental observation • Walking (endurance) • No improvement reported • Stairs (force) • No improvement • Hands strength • No improvement • 1x decline

20. Haelan 951 Parental observation • Energy • Improvement 4x • Learning, speaking • Better concentration 2x • Inflammation • No improvement

21. Haelan 951 Parental observation • Improved immunity • Faster regeneration after illnesses • Better sleeping • Better respiration

22. Haelan 951

23. Haelan 951

24. Haelan 951

25. Haelan 951

26. Haelan 951

27. 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

28. Ursodeoxycholic acid (UDCA)

29. Ursodeoxycholic acid (UDCA)