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.