barriers to treatment chip wilmot, md phd emory university
TRANSCRIPT
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Barriers to Treatment
Chip Wilmot, MD PhD
Emory University
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Disclosure
• Member, Data Safety Monitoring Board for studies involving Idebenone (Santhera Pharmaceuticals)
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“Why Don’t We Have A Treatment for Ataxia Yet?”
-anonymous at NAF AMM 2012
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“Why Don’t We Have A Treatment for Ataxia Yet?”
-anonymous at NAF AMM 2012and FAPG and GAASG
and my clinic and …
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“Why Don’t We Have A Treatment for Ataxia Yet?”
-Chip Wilmot, MD, PhDEmory University
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Treatment
the care and management of a patient to combat, ameliorate, or prevent a disease, disorder, or injury.
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Cure
A method or course of medical treatment used to restore health.
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Cure
A method or course of medical treatment used to restore health.
Don’t forget about prevention (at least for dominant SCA’s)
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Treatment
-Symptomatic -pain, cramps, depression, mobility
-Disease-modifying-slowing the rate of progression
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“Why Don’t We Have A Treatment for Ataxia Yet?”
-Developing a treatment is HARD
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“Why Don’t We Have A Treatment for Ataxia Yet?”
-Developing a treatment is HARD-Expectations for treatments can be unrealistic
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“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 …
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“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
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Clinical Disease
Treat Human Disease
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Clinical Disease
Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
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Clinical Disease
Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
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Clinical Disease
Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
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Clinical Disease
Treat Human Disease
Etiology (Cause)
Model Disease
Treat Model
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Clinical Disease
Etiology (Cause)
Model Disease
Treat Model
Treat Human DiseaseTreat Symptoms
Treat Disease
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What is needed to develop effective treatments?
1. Knowledge of the disease pathophysiology2. A way to measure the disease3. An understanding of the natural history of the
disease4. Research Infrastructure
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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
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What is needed to develop effective treatments?
1. Knowledge of the disease pathophysiology-the cause
-relevant models-mice, fruit flies, worms, etc.
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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
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FRDA Timeline
20001863 1980 1990 2010
First clinical description Gene Discovered
Outcome Measures Validated
Natural History Studies Begun
Treatment Trials
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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
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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
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What is needed to develop effective treatments?
1. All the preliminary info:-the cause-relevant models-candidate treatments
2. A way to measure the disease3. An understanding of the natural history of the disease
-rate of progression-variability
4. Research Infrastructure-ataxia centers-$$$-research subjects
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IS THIS TREATMENT EFFECTIVE?
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IS THIS TREATMENT EFFECTIVE?
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IS THIS TREATMENT EFFECTIVE?
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Copyright restrictions may apply.
Lynch, D. R. et al. Arch Neurol 2010;67:941-947.
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How can the likelihood of a positive trial be improved?
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How can the likelihood of a positive trial be improved?
1. Reduce variability-large numbers-homogeneous study population-precise measures
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How can the likelihood of a positive trial be improved?
1. Reduce variability-large numbers-homogeneous study population-precise measures
2. Increase trial timeline
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How can the likelihood of a positive trial be improved?
1. Reduce variability-large numbers-homogeneous study population-precise measures
2. Increase trial timeline3. Use a more effective treatment
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How can the likelihood of a positive trial be improved?
1. Reduce variability-large numbers-homogeneous study population-precise measures
2. Increase trial timeline3. Use a more effective treatment
Note: These are not always possible
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What can be done to facilitate treatment
development?
1. Learn from other diseases
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ALS
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ALS vs. ataxia-ALS is 90% sporadic; pathophysiology not well understood-Quicker progression, more definite clinical measures
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What can be done to facilitate treatment
development?
1. Learn from other diseases2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available
-(e.g. ALS PEG tubes and ventilatory support)
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What can be done to facilitate treatment
development?
1. Learn from other diseases2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available
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What can be done to facilitate treatment
development?
1. Learn from other diseases2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available3. Never underestimate the power of dedicated action
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What can be done to facilitate treatment
development?
1. Learn from other diseases2. Don’t disregard low lying fruit!!!
-non-sexy treatments ARE available3. Never underestimate the power of dedicated action
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Thanks
-Patients, families-Coordinators: Bettye Robinson RN, Sue Gronka RN-Colleagues-NAF, FARA, MDA, NIH