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Amyotrophic lateral sclerosis: Recent advances and future therapies

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London and National Hospital for Neurology and Neurosurgery, London, UK.
Current Opinion in Neurology (Impact Factor: 5.73). 01/2006; 18(6):712-9. DOI: 10.1097/01.wco.0000187248.21103.c5
Source: PubMed

ABSTRACT Amyotrophic lateral sclerosis is a rare but fatal motoneuron disorder. Despite intensive research riluzole remains the only available therapy, with only marginal effects on survival. Here we review some of the recent advances in the search for a disease-modifying therapy for amyotrophic lateral sclerosis.
A number of established agents have recently been re-investigated for their potential as neuroprotective agents, including beta-lactam antibiotics and minocycline. Progress has also been made in exploiting growth factors for the treatment of amyotrophic lateral sclerosis, partly due to advances in developing effective delivery systems to the central nervous system. A number of new therapies have also been identified, including a novel class of compounds, heat-shock protein co-inducers, which upregulate cell stress responses thereby mediating neuroprotection. Non-drug-based therapies are also under development, with progress in gene-silencing and stem cell therapies.
In the past few years, significant advances have been made in both our understanding of amyotrophic lateral sclerosis pathogenesis and the development of new therapeutic approaches. However, caution must be exercised in view of the long-standing failure to successfully transfer therapeutic compounds to the clinic. A deeper awareness in the research community of the need for clinically relevant preclinical studies, coupled with a better understanding of the issues surrounding clinical trial design for amyotrophic lateral sclerosis, offers hope that the growing list of validated preclinical therapeutics can finally yield an effective disease-modifying treatment.

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    • "sporadic form of ALS remains unclear, while progresses in understanding the mechanisms of disease have been made into the familial forms. Glutamate excitotoxicity, oxidative stress, microglial activation, and neuroinflammation have all been implicated in the pathogenesis of ALS (Bendotti and Carrı`, 2004; Bruijn et al., 2004; Nirmalananthan and Greensmith, 2005; Rao and Weiss, 2004). Interestingly, these pathological events are potentially modulated by endocannabinoids, possibly explaining the neuroprotective eVects of increasing endocannabinoid levels in ALS animal models. "
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    • "Currently, riluzole (Rilutek ® ) is the only drug treatment for ALS approved by the Food and Drug Administration (FDA). However, the drug only slows progression of ALS rather than curing the disease (Bruijn, Miller et al. 2004; Nirmalananthan and Greensmith 2005). Therefore, new treatment options are greatly needed for this devastating disease. "
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