New therapeutic targets for amyotrophic lateral sclerosis.
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological disorders, affecting approximately half a million people worldwide. Currently there is no cure or prevention for ALS. Although ALS is a rare condition, it places a tremendous socioeconomic burden on patients, family members, caregivers and health systems.


METHODS
The review examines the mechanisms that may contribute to motor neuron degeneration in ALS, among which oxidative damage, glutatamate excitoxicity, mitochondrial dysfunction, impaired axonal transport, apoptotic cell death, growth factor deficiency, glial cell pathology and abnormal RNA metabolism are potential targets for ALS treatment. The article provides an overview of clinical trials performed to date in attempts to treat ALS with regard to molecular mechanisms and pathways they act on. It also discusses new trials based on recently developed molecular biology techniques.


CONCLUSIONS
Despite significant effectiveness of several potential therapeutics observed in preclinical trials, the results were not translatable to patients with ALS. The development of effective treatments of ALS strictly depends on understanding the primary cause of the disease. This goal will only be achieved when we identify the trigger point for motor neuron death in ALS.
Medical University of Warsaw, Department of Neurology, Banacha 1a, 02-097 Warsaw, Poland.
Magdalena
M
Kuzma-Kozakiewicz
Hubert
H
Kwiecinski
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D058990:Molecular Targeted Therapy; D009046:Motor Neurons / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation
D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering