1. Chip Wilmot, MD PhD Emory University
Barriers to Treatment
Chip Wilmot, MD PhD
Emory University

2. Disclosure
Member, Data Safety Monitoring Board for studies involving Idebenone (Santhera Pharmaceuticals)

3. “Why Don’t We Have A Treatment for Ataxia Yet?”
-anonymous at NAF AMM 2012

4. “Why Don’t We Have A Treatment for Ataxia Yet?”
-anonymous at NAF AMM 2012
and FAPG and GAASG
and my clinic and …

5. “Why Don’t We Have A Treatment for Ataxia Yet?”
-Chip Wilmot, MD, PhD
Emory University

6. Treatment
the care and management of a patient to combat, ameliorate, or prevent a disease, disorder, or injury.

7. Cure
A method or course of medical treatment used to restore health.

8. Cure A method or course of medical treatment used to restore health.
Don’t forget about prevention (at least for dominant SCA’s)

9. Treatment -Symptomatic -pain, cramps, depression, mobility
-Disease-modifying
-slowing the rate of progression

10. “Why Don’t We Have A Treatment for Ataxia Yet?”
-Developing a treatment is HARD

11. “Why Don’t We Have A Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be unrealistic

12. “Why Don’t We Have A Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be unrealistic
-We are doing a good job, but …

13. “Why Don’t We Have A Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be unrealistic
-We are doing a good job, but …
- … there are certainly ways to facilitate treating ataxia

14. Clinical Disease
Treat Human Disease

15. Clinical Disease Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease

16. Clinical Disease Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease

17. Clinical Disease Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease

18. Clinical Disease Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease

19. Clinical Disease Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Symptoms
Treat Human Disease
Treat Disease

20. What is needed to develop effective treatments?
Knowledge of the disease pathophysiology
A way to measure the disease
An understanding of the natural history of the disease
Research Infrastructure

21. -the cause – What is needed to develop effective treatments?
Knowledge of the disease pathophysiology
-the cause –
-ataxia genes galore
-downstream consequences, e.g mitochondrial dysfunction in FRDA
-insights into cerebellar (dys)function

22. -relevant models What is needed to develop effective treatments?
Knowledge of the disease pathophysiology
-the cause
-relevant models
-mice, fruit flies, worms, etc.

23. -candidate treatments
What is needed to develop effective treatments?
Knowledge of the disease pathophysiology
-the cause
-relevant models
-candidate treatments
-EPI-743, pioglitazone, lithium, riluzole, VEGF

25. FRDA Timeline 1863 1980 1990 2000 2010 Treatment Trials
Natural History Studies Begun
Outcome Measures Validated
First clinical description
Gene Discovered
1863
1980
1990
2000
2010

26. A way to measure the disease
What is needed to develop effective treatments?
Knowledge of the disease pathophysiology
-the cause
-relevant models
-candidate treatments
A way to measure the disease
-clinical scales, instrumented measures, biomarkers

27. What is needed to develop effective treatments?
All the preliminary info:
-the cause
-relevant models
-candidate treatments
A way to measure the disease
An understanding of the natural history of the disease
-rate of progression
-variability

28. What is needed to develop effective treatments?
All the preliminary info:
-the cause
-relevant models
-candidate treatments
A way to measure the disease
An understanding of the natural history of the disease
-rate of progression
-variability
Research Infrastructure
-ataxia centers
-$$$
-research subjects

29. IS THIS TREATMENT EFFECTIVE?

30. IS THIS TREATMENT EFFECTIVE?

31. IS THIS TREATMENT EFFECTIVE?

32. Lynch, D. R. et al. Arch Neurol 2010;67:941-947.
Copyright restrictions may apply.

33. How can the likelihood of a positive trial be improved?

34. How can the likelihood of a positive trial be improved?
1. Reduce variability
-large numbers
-homogeneous study population
-precise measures

35. How can the likelihood of a positive trial be improved?
1. Reduce variability
-large numbers
-homogeneous study population
-precise measures
2. Increase trial timeline

36. How can the likelihood of a positive trial be improved?
1. Reduce variability
-large numbers
-homogeneous study population
-precise measures
2. Increase trial timeline
3. Use a more effective treatment

37. How can the likelihood of a positive trial be improved?
1. Reduce variability
-large numbers
-homogeneous study population
-precise measures
2. Increase trial timeline
3. Use a more effective treatment
Note: These are not always possible

38. What can be done to facilitate treatment development?
1. Learn from other diseases

39. ALS

40. ALS vs. ataxia
ALS is 90% sporadic; pathophysiology not well understood
Quicker progression, more definite clinical measures

42. What can be done to facilitate treatment development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available
-(e.g. ALS PEG tubes and
ventilatory support)

45. What can be done to facilitate treatment development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available

46. What can be done to facilitate treatment development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available
3. Never underestimate the power of dedicated action

47. What can be done to facilitate treatment development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available
3. Never underestimate the power of dedicated action

51. Thanks -Patients, families
-Coordinators: Bettye Robinson RN, Sue Gronka RN
-Colleagues
-NAF, FARA, MDA, NIH