Saving Nerves if People take their drugs

Gnanapavan S, Grant D, Morant S, Furby J, Hayton T, Teunissen CE, Leoni V, Marta M, Brenner R, Palace J, Miller DH, Kapoor R, Giovannoni G. Biomarker report from the phase II lamotrigine trial in secondary progressive MS - neurofilament as a surrogate of disease progression.PLoS One. 2013 Aug 1;8(8):e70019. doi: 10.1371/journal.pone.0070019.

OBJECTIVE: Lamotrigine trial in SPMS was a randomised control trial to assess whether partial blockade of sodium channels has a neuroprotective effect. The current study was an additional study to investigate the value of neurofilament (NfH) and other biomarkers in predicting prognosis and/or response to treatment.
METHODS:SPMS patients who attended the NHNN or the Royal Free Hospital, UK, eligible for inclusion were invited to participate in the biomarker study. Primary outcome was whether lamotrigine would significantly reduce detectable serum NfH at 0-12, 12-24 and 0-24 months compared to placebo. Other serum/plasma and CSF biomarkers were also explored.
RESULTS:Treatment effect by comparing absolute changes in NfH between the lamotrigine and placebo group showed no difference, however based on serum lamotrigine adherence there was significant decline in NfH (NfH 12-24 months p=0.043, Nfh 0-24 months p=0.023). Serum NfH correlated with disability: walking times, 9-HPT (non-dominant hand), PASAT, z-score, MSIS-29 (psychological) and EDSS and MRI cerebral atrophy and MTR. Other biomarkers explored in this study were not found to be significantly associated, aside from that of plasma osteopontin.
CONCLUSIONS:The relations between NfH and clinical scores of disability and MRI measures of atrophy and disease burden support NfH being a potential surrogate endpoint complementing MRI in neuroprotective trials and sample sizes for such trials are presented here. We did not observe a reduction in NfH levels between the Lamotrigine and placebo arms, however, the reduction in serum NfH levels based on lamotrigine adherence points to a possible neuroprotective effect of lamotrigine on axonal degeneration.


In response to a comment posted yesterday, I was hunting for this post on the blog but could not seem to find it, so I post it again. 

As it will help with the Altimetrics ...Ho Ho.

What does this study say well if you talk to any neuro they will tell you that Lamotrigine was tried in progressive MS and it failed.

http://multiple-sclerosis-research.blogspot.com/2011/09/research-lamotrigine-fails-as.html

What this study does is test to see whether people on the trial were taking their drugs. So they looked at the packets of pills and they could see that 40% of people weren't taking their pills and then they measured the blood and found that 50% of people were not taking their meds.  The original animal work reporting a beneficial effects was poo-pooed by the neuros because the trial failed...so how would a trial ever work when only 50% of people were not taking their drugs? So the solid basic science gets binned because of dodgy clinical work.

The reason why people were not taking their meds is probably because of side effects.

However if you look at nerve proteins in the blood in the people who took their drugs verses those that didn't and you got a significant difference. There was less nerve proteins in people taking their drugs....suggesting less nerve damage (which would release the nerve proteins so they could be picked up in the blood).
This suggests that maybe Lamotrigine was slowing nerve loss

This suggests that the basic science was not such a load of bollony. However the failed trial, will doom development. However, we have taken other drugs in this class to see if they can protect nerves from damage. This is the basis of the PROXIMUS trial that we are doing.

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