Neuroprotective agents for clinical trials in ALS: a systematic assessment.
BACKGROUND
Riluzole is currently the only Food and Drug Administration-approved treatment for ALS, but its effect on survival is modest.


OBJECTIVE
To identify potential neuroprotective agents for testing in phase III clinical trials and to outline which data need to be collected for each drug.


METHODS
The authors identified 113 compounds by inviting input from academic clinicians and researchers and via literature review to identify agents that have been tested in ALS animal models and in patients with ALS. The list was initially narrowed to 24 agents based on an evaluation of scientific rationale, toxicity, and efficacy in previous animal and human studies. These 24 drugs underwent more detailed pharmacologic evaluation.


RESULTS
Twenty drugs were selected as suitable for further development as treatments for patients with ALS. Talampanel and tamoxifen have completed early phase II trials and have demonstrated preliminary efficacy. Other agents (ceftriaxone, minocycline, ONO-2506, and IGF-1 polypeptide) are already in phase III trials involving large numbers of patients with ALS. Remaining agents (AEOL 10150, arimoclomol, celastrol, coenzyme Q10, copaxone, IGF-1-viral delivery, memantine, NAALADase inhibitors, nimesulide, scriptaid, sodium phenylbutyrate, thalidomide, trehalose) require additional preclinical animal data, human toxicity and pharmacokinetic data including CNS penetration prior to proceeding to large scale phase III human testing. Further development of riluzole analogues should be considered.


CONCLUSIONS
Several potential neuroprotective compounds, representing a wide range of mechanisms, are available and merit further investigation in ALS.
Traynor
B J
BJ
Neurology Clinical Trials Unit, Department of Neurology, Massachusetts General Hospital, Boston, USA. traynorb@mail.nih.gov
Bruijn
L
L
Conwit
R
R
Beal
F
F
O'Neill
G
G
Fagan
S C
SC
Cudkowicz
M E
ME
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods*; D005069:Evaluation Studies as Topic; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care
D018696:Neuroprotective Agents