Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis.
It has been > 130 years since the first description of the upper and lower motor neuron disease called amyotropic lateral sclerosis (ALS). Sadly, there has been little change in the long interval over which this disease is diagnosed, or in its poor prognosis. Significant gains have been made, however, in understanding its pathophysiology and in symptomatic care. Disease-causing mutations have been identified and used to create animal models. Other identified mutations may increase susceptibility and cause disease only in a particular environment and at a particular age. A number of 'downstream' molecular pathways have been implicated, including transcriptional disturbances, protein aggregation, excitotoxicity, mitochondrial dysfunction, oxidative stress, neuroinflammation, cytoskeletal and axonal transport derangements, growth factor dysregulation and apoptosis. This knowledge has led to an impressive pipeline of candidate therapies that offer hope for finally being able to alter ALS disease progression. These are described and prioritized herein, and suggestions are offered for efficiently sifting through them.
Bedlack
Richard S
RS
Duke University Medical Center, Box 3333, Durham NC 27705, USA. bedla001@mc.duke.edu
Traynor
Bryan J
BJ
Cudkowicz
Merit E
ME
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D006801:Humans; D016472:Motor Neuron Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents