Multiple Sclerosis Research: Symptomatic drugs may slow your progression

Drugs that control MS symtoms have been reported to be neuroprotective in models of MS and so they should slow progression.

I say NSS this is what we have been saying for a long time,

Hundehege P, Fernandez-Orth J, Römer P, Ruck T, Müntefering T, Eichler S, Cerina M, Epping L, Albrecht S, Menke AF, Birkner K, Göbel K, Budde T, Zipp F, Wiendl H, Gorji A, Bittner S, Meuth SG.Targeting Voltage-Dependent Calcium Channels with Pregabalin Exerts a Direct Neuroprotective Effect in an Animal Model of Multiple Sclerosis.Neurosignals. 2018 Nov 27;26(1):77-93

BACKGROUND/AIMS:Multiple sclerosis (MS) is a prototypical autoimmune central nervous system (CNS) disease. Particularly progressive forms of MS (PMS) show significant neuroaxonal damage as consequence of demyelination and neuronal hyperexcitation. Immuno-modulatory treatment strategies are beneficial in relapsing MS (RMS), but mostly fail in PMS. Pregabalin (Lyrica®) is prescribed to MS patients to treat neuropathic pain. Mechanistically, it targets voltage-dependent Ca2+ channels and reduces harmful neuronal hyperexcitation in mouse epilepsy models. Studies suggest that GABA analogues like pregabalin exert neuroprotective effects in animal models of ischemia and trauma.

METHODS:We tested the impact of pregabalin in a mouse model of MS (experimental autoimmune encephalomyelitis, EAE) and performed histological and immunological evaluations as well as intravital two-photon-microscopy of brainstem EAE lesions.
RESULTS:Both prophylactic and therapeutic treatments ameliorated the clinical symptoms of EAE and reduced immune cell infiltration into the CNS. On neuronal level, pregabalin reduced long-term potentiation in hippocampal brain slices indicating an impact on mechanisms of learning and memory. In contrast, T cells, microglia and brain endothelial cells were unaffected by pregabalin. However, we found a direct impact of pregabalin on neurons during CNS inflammation as it reversed the pathological elevation of neuronal intracellular Ca2+ levels in EAE lesions.
CONCLUSION:The presented data suggest that pregabalin primarily acts on neuronal Ca2+ channel trafficking thereby reducing Ca2+-mediated cytotoxicity and neuronal damage in an animal model of MS. Future clinical trials need to assess the benefit for neuronal survival by expanding the indication for pregabalin administration to MS patients in further disease phases.

This study looks at pregabalin which is a drug that affects calcium levels. Too much calcium in a nerve like too much sodium in a nerve causes over excitation and over excitation of the nerve can lead to cell death. So blocking the calcium as done here or with sodium channel blockers can slow the accumulation of these ions into the cell and can stop nerve cell death as a consequence of the inflammatory insult. First you have to be careful with the experiments because these types of drugs can knock the animals out and sedate them. This is stressful and this is immunosuppressive and if you have immunosuppression you do not get lesions and so you do not lose nerves. The doses used here were immunosuppressive as cell infiltration is inhibited and therefore it has to be neuroprotective. Ath eh rest them become fluff. Is there any evidence that pregabalin is immunosuppressive and blocks relapses, I doubt it. We have shown that sodium channel blockers and cannabinonids that also block excitation are neuroprotective without being immunosuppressive. We also asked the question would GABA B stimulation with baclofen do the same. You would think so as it is a G protein-coupled receptor that activates to block calcium channels and affects potassium channels to block nerve excitability, so it too must be neuroprotective. However you ask is there any evidence that baclofen or pregabalin for that matter slow progression and the answer from the neuros I have asked is that we have no idea as we do not have the data.

So will people do a trial maybe, maybe not. No company is going to do it. I also thought why develop symptomatic drugs with neuroprotective potential. A symptom control trial is quick compared to a neuroprotective trial. However, the price for a symtomatic drug is to be compared to the cost of baclofencosting pence and not a disease modifying drugs costing thousands, so you would not want a symptomatic label if you are developing drugs...sad but true.