The epidemiology and treatment of ALS: focus on the heterogeneity of the disease and critical appraisal of therapeutic trials.
Abstract Effective treatments for amyotrophic lateral sclerosis (ALS) have remained elusive. Only riluzole, a drug thought to affect glutamate metabolism, improves survival albeit to modest extent. Explanations for the negative results of therapeutic trials include a likely heterogeneity, both in disease susceptibility and pathogenic mechanisms, and faulty methodology of clinical trials. Further understanding of these factors will lead to improvements in patient stratification, and in the design of future clinical trials.
Beghi
Ettore
E
Istituto di Ricerche Farmacologiche "Mario Negri", Via G. la Masa 19, 20156 Milano, Italy. ettore.beghi@marionegri.it
Chiò
Adriano
A
Couratier
Philippe
P
Esteban
Jesùs
J
Hardiman
Orla
O
Logroscino
Giancarlo
G
Millul
Andrea
A
Mitchell
Douglas
D
Preux
Pierre-Marie
PM
Pupillo
Elisabetta
E
Stevic
Zorica
Z
Swingler
Robert
R
Traynor
Bryan J
BJ
Van den Berg
Leonard H
LH
Veldink
Jan H
JH
Zoccolella
Stefano
S
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism / Q000628:therapy*; D000975:Antioxidants / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004750:Enteral Nutrition; D005060:Europe / Q000453:epidemiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015994:Incidence; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D012107:Research Design; D012121:Respiration, Artificial; D019782:Riluzole / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data
D000975:Antioxidants; D036341:Intercellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D019782:Riluzole