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 2012and FAPG and GAASG

and my clinic and …

“Why Don’t We Have A Treatment for Ataxia Yet?”

-Chip Wilmot, MD, PhDEmory 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

Treat Human Disease

Etiology (Cause)

Model Disease

Treat Model

Clinical Disease

Treat Human Disease

Etiology (Cause)

Model Disease

Treat Model

Clinical Disease

Treat Human Disease

Etiology (Cause)

Model Disease

Treat Model

Clinical Disease

Treat Human Disease

Etiology (Cause)

Model Disease

Treat Model

Clinical Disease

Etiology (Cause)

Model Disease

Treat Model

Treat Human DiseaseTreat Symptoms

Treat Disease

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

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

20001863 1980 1990 2010

First clinical description Gene Discovered

Outcome Measures Validated

Natural History Studies Begun

Treatment Trials

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 disease3. 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?

Copyright restrictions may apply.

Lynch, D. R. et al. Arch Neurol 2010;67:941-947.

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 timeline3. 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 timeline3. 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 diseases2. 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 diseases2. Don’t disregard low lying fruit!!!

-non-sexy treatments ARE available

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

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

Thanks

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