Kanai K et a. Motor axonal excitability properties are strong predictors for survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2012 May 7 [Epub].
OBJECTIVE: The aim of this study was to investigate whether axonal excitability indices are associated with survival in patients with amyotrophic lateral sclerosis (ALS=Motor neuron disease in UK and Lou Gerhig's disease in USA). Previous nerve excitability studies suggested increased persistent sodium currents in motor axons of patients with ALS, which lead to axonal hyperexcitability (Overactivation of nerve) and potentially enhance neuronal death.
METHODS: 112 patients with sporadic ALS were followed up until endpoint (death or tracheostomy). Multivariate analyses were performed using the Cox proportional hazard model. Threshold tracking was used to measure multiple axonal excitability indices in median motor axons, such as strength-duration time constant (SDTC; a measure of nodal persistent sodium current). Latent addition was also used to estimate the magnitude of persistent sodium currents.
RESULTS:The overall median tracheostomy-free survival from onset was 37 months. Prolonged SDTC was strongly associated with shorter survival (adjusted HR 4.07; 95% CI 1.7 to 9.8; p=0.0018) compared with older onset age (>60 years; HR=1.80) and bulbar onset (HR=1.80). Estimated median survival was 34 months in the longer SDTC group and 51 months in the shorter SDTC group. This index was highly statistically significant even after multiple testing adjustments with age and site of onset (bulbar or limb). Latent addition study results were consistent with these findings.
CONCLUSIONS. Axonal persistent sodium currents, estimated by SDTC and latent addition, are strong and independent predictors for shorter survival in patients with ALS. Membrane hyperexcitability is possibly associated with motor neuronal death, and modulation of excessive sodium currents could be a novel therapeutic option for ALS.
It is thought the demyelination in MS can be associated with problems of sodium channels and sodium loading. Furthermore over stimulation of the nerve is thought to lead to excitotoxicity. Although ALS and MS, have different causation, excititoxicity is thought to be a problem in both MS and ALS. ALS is a more aggressive disease than MS so things are more easy to detect. However, there is, but there is one drug (Riluzole) that is licenced for ALS. Could it have any benefit in progressive MS there is an indication that it could do..
Killestein J, Kalkers NF, Polman CHGlutamate inhibition in MS: the neuroprotective properties of riluzole. J Neurol Sci. 2005;233:113-5.
In addition to demyelination and damage to oligodendrocytes, axonal injury and neuronal cell death are dominating histopathological characteristics of multiple sclerosis (MS). Still little is known about the cause of the damage. Extracellular accumulation of glutamate contributes to excitotoxic injury of neurons and glial cells, suggesting that the maintenance of subtoxic extracellular glutamate levels may be crucial. Riluzole is a neuroprotective agent that inhibits the release of glutamate from nerve terminals and modulates glutamate, i.e., kainate and NMDA receptors. It inhibits excitotoxic injury in several experimental models of neurodegenerative disease. We performed a small run-in versus treatment MR-monitored pilot study in 16 primary progressive MS patients. The results suggest that riluzole reduces the rate of cervical cord atrophy and the development of T1 hypointense lesions on magnetic resonance imaging in primary progressive MS. The rate of brain atrophy was only slightly decreased. The results indicate an effect on mechanisms involving lesion evolution and axonal loss, but no clear effect on new lesion formation. However, the data suffer from several limitations and must be confirmed in future trials.
Hopefully these studies will get done soon, it is only ten years since these initial investigator led studies....All I can say is "Shame on You Pharma" as this could have been looked at many, many years ago. It probably is not great but perhaps it could do something positive and slow down progressive MS.