The heterogeneity of amyotrophic lateral sclerosis: a possible explanation of treatment failure.
Amyotrophic lateral sclerosis (ALS) is a severe clinical condition characterized by upper and lower motor neuron degeneration for which there is no truly effective treatment. The absence of an effective treatment can be explained in part by the complex and heterogeneous genetic, biochemical, and clinical features of ALS. While ALS accounts for the majority of the motor neuron diseases, the recognition of disease variants and mimic syndromes may lead to further insights into possible causes for the generality of ALS. From a biochemical perspective, the process of motor neuron degeneration is complex and the multifactorial influences and potential biomarkers of ALS have never been assessed in the light of the clinical heterogeneity of ALS. Several genes and environmental influences have been suggested as possible risk factors of ALS. A better understanding of interactions between these risk factors, potential biomarkers and heterogeneous clinical features may lead to more clearly defined pathological profiles among individuals or groups of ALS patients and in turn lead to more focused therapeutic trials.
Beghi
Ettore
E
Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy. beghi@marionegri.it
Mennini
Tiziana
T
Bendotti
Caterina
C
Bigini
Paolo
P
Logroscino
Giancarlo
G
Chiò
Adriano
A
Hardiman
Orla
O
Mitchell
Douglas
D
Swingler
Robert
R
Traynor
Bryan J
BJ
Al-Chalabi
Ammar
A
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000453:epidemiology; D000818:Animals; D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D006801:Humans; D016896:Treatment Outcome
D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists