MIGRAINE HEADACHE

1
8-10 December 2005 in Dublin, Republic of Ireland
2
8-10 December 2005 in Dublin, Republic of Ireland

• New elements in understanding ALS and ALS
  clinical trials design
• Results of clinical trials in humans
• Future directions

3
8-10 December 2005 in Dublin, Republic of Ireland
Neurophysiology and Imaging in ALS

• Motor unit estimation in ALS
• Cortical dysfunction in ALS (MEG, imaging,
  autonomic system)
• Better understanding the disease
• Better care of ALS patients

4
8-10 December 2005 in Dublin, Republic of Ireland
Exploring the link between ALS and impaired
cognition

• Prevalence More common than we think
• Detection Neuropsych, brain imaging, genetic
  study etc.
• Management issues Patient, family, care providers

5
8-10 December 2005 in Dublin, Republic of Ireland
Exploring the link between ALS and impaired
cognition

• Premorbid personality in ALS
• Frontotemporal dementia and ALS

6
8-10 December 2005 in Dublin, Republic of Ireland
Phenotypic variants of ALS
Clinical and laboratory findings help determine
the variant forms

• Limb-onset, bulbar onset etc.
• Age of onset and gender
• Cognitive impairment
• Familial ALS
• Other confounding genes and environment
• ALS mimics Kennedys disease, HSP etc.

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8-10 December 2005 in Dublin, Republic of Ireland
Smarter design of ALS treatment trials

• New phase II design to improve clinical trials
• Shorter clinical trial in rapidly progressive ALS

8
8-10 December 2005 in Dublin, Republic of Ireland
Alternative treatments and ALS Separating hope
from hype

• Genuine
• Experimental
• Questionable

http//www.quackwatch.org/
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8-10 December 2005 in Dublin, Republic of Ireland

• Phase II/III trial of TCH 346 in ALS
• Nearly 600 patients
• Primary outcome measure ALSFRS-R
• Secondary outcome measures Survival, FVC, MVIC
• Powered to detect a 25 reduction in decline
• Results
• Negative study
• Novel study design (16 week natural hx lead-in
  phase)

10
8-10 December 2005 in Dublin, Republic of Ireland

• Creatine trial in ALS (Rosenfeld et al, USA)
• Over 100 patients
• 10 G for 5 days then 5 G daily for 9 months
• Primary outcome measures Muscle strength (MVIC)
  and muscle fatigue index
• Secondary outcome measures ALSFRS, FVC, QoL
• Results
• Safe and well tolerated
• Not effective

11
8-10 December 2005 in Dublin, Republic of Ireland

• Phase IIB Tamoxifen clinical trial in ALS (Brooks
  et al, USA)
• Safe
• Well tolerated
• Survival benefit in Riluzole-treated patients

12
8-10 December 2005 in Dublin, Republic of Ireland

• Phase II trial of glatiramir acetate (Copaxone)
  in ALS (Columbia group, USA)
• 30 patients
• 20 mg daily and bi-weekly injections
• Phase II trial of INF-1A in ALS (Simpson et al,
  USA)
• Results
• Safe
• Well tolerated
• Robust T-cell mediated immune response (Columbia)

13
8-10 December 2005 in Dublin, Republic of Ireland

• Stem Cell Research

14
8-10 December 2005 in Dublin, Republic of Ireland

• Satellite research group meetings
• Arimoclomol clinical trial (CytRx)
• NEALS research group meeting (Ceftriaxone)
• ALSRG meeting (DNA banking and genetic
  association studies)

15
8-10 December 2005 in Dublin, Republic of Ireland

• Summary
• Results of clinical trials
• Research based on the mechanism of disease
• Future clinical trials in ALS