Barriers to Treatment
Chip Wilmot, MD PhD
Emory University
Disclosure
• Member, Data Safety Monitoring Board
for studies involving Idebenone
(Santhera Pharmaceuticals)
“Why Don’t We Have A
Treatment for Ataxia Yet?”
-anonymous at NAF AMM 2012
“Why Don’t We Have A
Treatment for Ataxia Yet?”
-anonymous at NAF AMM 2012
and FAPG and GAASG
and my clinic and …
“Why Don’t We Have A
Treatment for Ataxia Yet?”
-Chip Wilmot, MD, PhD
Emory University
Treatment
the care and management of a
patient to combat, ameliorate, or
prevent a disease, disorder, or injury.
Cure
A method or course of medical
treatment used to restore health.
Cure
A method or course of medical
treatment used to restore health.
Don’t forget about prevention (at
least for dominant SCA’s)
Treatment
-Symptomatic
-pain, cramps, depression, mobility
-Disease-modifying
-slowing the rate of progression
“Why Don’t We Have A
Treatment for Ataxia Yet?”
-Developing a treatment is HARD
“Why Don’t We Have A
Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be
unrealistic
“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 …
“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
Clinical Disease
Treat Human Disease
Clinical Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease
Clinical Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease
Clinical Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease
Clinical Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human Disease
Clinical Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Symptoms
Treat Human Disease
Treat Disease
What is needed to develop effective
treatments?
1. Knowledge of the disease pathophysiology
2. A way to measure the disease
3. An understanding of the natural history of the
disease
4. Research Infrastructure
What is needed to develop effective
treatments?
1. Knowledge of the disease pathophysiology
-the cause –
-ataxia genes galore
-downstream consequences, e.g
mitochondrial dysfunction in FRDA
-insights into cerebellar (dys)function
What is needed to develop effective
treatments?
1. Knowledge of the disease pathophysiology
-the cause
-relevant models
-mice, fruit flies, worms, etc.
What is needed to develop effective
treatments?
1. Knowledge of the disease pathophysiology
-the cause
-relevant models
-candidate treatments
-EPI-743, pioglitazone, lithium,
riluzole, VEGF
FRDA Timeline
Treatment Trials
Natural History
Studies Begun
Outcome
Measures
Gene Discovered Validated
First clinical
description
1863
1980
1990
2000
2010
What is needed to develop effective
treatments?
1. Knowledge of the disease pathophysiology
-the cause
-relevant models
-candidate treatments
2.A way to measure the disease
-clinical scales, instrumented
measures, biomarkers
What is needed to develop effective
treatments?
1. All the preliminary info:
-the cause
-relevant models
-candidate treatments
2. A way to measure the disease
3. An understanding of the natural
history of the disease
-rate of progression
-variability
What is needed to develop effective
treatments?
1. All the preliminary info:
-the cause
-relevant models
-candidate treatments
2. A way to measure the disease
3. An understanding of the natural history of the disease
-rate of progression
-variability
4. Research Infrastructure
-ataxia centers
-$$$
-research subjects
IS THIS TREATMENT EFFECTIVE?
IS THIS TREATMENT EFFECTIVE?
IS THIS TREATMENT EFFECTIVE?
Lynch, D. R. et al. Arch Neurol 2010;67:941-947.
Copyright restrictions may apply.
How can the likelihood of a
positive trial be improved?
How can the likelihood of a
positive trial be improved?
1. Reduce variability
-large numbers
-homogeneous study population
-precise measures
How can the likelihood of a
positive trial be improved?
1. Reduce variability
-large numbers
-homogeneous study population
-precise measures
2. Increase trial timeline
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
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
What can be done to
facilitate treatment
development?
1. Learn from other diseases
ALS
ALS vs. ataxia
-ALS is 90% sporadic; pathophysiology
not well understood
-Quicker progression, more definite
clinical measures
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)
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
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
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
Thanks
-Patients, families
-Coordinators: Bettye Robinson RN, Sue Gronka RN
-Colleagues
-NAF, FARA, MDA, NIH