ProfG has been banging-on about “Treat early and effectively to save brain”, until he is blue in the face….So much so, that he has turned into a Smurf
Sadly there are still many of his colleagues that don’t buy into this… and follow the mantra of “There….There, we’ll get ya a nice wheel chair”
The vast majority of neuros and pharma bods still cling-on to the notion that single drug treatment is the only way to go.
The therapeutic pyramid has not been built in the minds of the masses.
Why do I say this?
Look at all the clinical trials that academics do…MS-“NOT SO” SMART is a good example. Three neuroprotectives against placebo and doing nothing about the inflammatory component….It failed so it was not so smart…STAT-2 follows STAT MS and looks at a neuroprotective but not on top of a disease modifying treatment. What will happen if MS-SMART-2 comes along?….Combination or more of the same I suspect. We can blame those people for making the wrong choice of drug to justify another go, but god forbid if we have the wrong type of trial design. If it is it fails each time and we have not learned for past mistakes
However, time is running out. The progressive MS space is getting filled with DMT and neuroprotectives/remyelination agents will have to go on top of these. I say great and about time.
However ProfG has also been making the case that MS is one disease and it is not relapsing MS on one day and the next day it is progressive M.
Nerve loss and damage occurs at the begining to the end of MS. Therefore we should consider a neuroprotectant at the beginning of MS as well as the end. OK the problem is I can’t say definitively which agent, but we have to make a start before ProfG turns into Papa Smurf.
The phenyton optic neuritis trial indicated benefit from early treatment with a neuroprotective, but it never went anywhere and clinical practise has not changed. But maybe you do need protection and repair agents all the way through MS and certainly at the beginning when there is something to save. Indeed it is most important right at the beginning.
Why? Because this is when you have what we call “neurological reserve”. You can afford to loose a few nerves before you notice anything, but once you reach that point every nerve that is lost can be important.People with PPMS have used up their reserve quickly.
It is not just MS. You can lose about 80% of your pancreas before you notice type 1 diabetes.
Currently you can’t grow a brain so best not to lose it.
What more do you need?…..Evidence?….How much more do you need?
Axonal Degeneration Independent of Inflammatory Activity: Is It More Intense in the Early Stages of Relapsing-Remitting Multiple Sclerosis Disease? Cilingir V, Batur M.Eur Neurol. 2020 Sep 21:1-9. doi: 10.1159/000510116. Online ahead of print.
Background: This study aimed to investigate whether there are differences in the axonal degeneration rate between patients in the early years of relapsing-remitting multiple sclerosis (RRMS) disease and RRMS patients in their later years.
Methods: The early-stage RRMS patients (EMS) group had 65 patients whose duration of disease was within 3 years from the date of the first attack. The late-stage RRMS patients (LMS) group had 69 patients whose duration of disease was within the range of 3-10 years from the date of the first attack. In addition, a control group was composed of 32 healthy subjects. Peripapillary retinal nerve fiber layer (RNFL) thickness was monitored with spectral-domain OCT in all included patients for approximately 3 years.
Results: The annual RNFL atrophy rate (aRNFLr) in the EMS group was -1.246 ± 0.778 μm/year, the aRNFLr in the LMS group was -0.898 ± 0.536 μm/year, and the aRNFLr was -0.234 ± 0.154 μm/year in the control group (p < 0.001). The aRNFLr in the EMS group was significantly higher than the aRNFLr in the LMS group (p = 0.01). The aRNFLr was not associated with MRI activity or the condition of having an attack. There was a correlation between Expanded Disability Status Scale (EDSS) progression and aRNFLr in both the EMS and LMS patient groups (r = -0.471, p < 0.001, and r = -0.567, p < 0.001, respectively).
Conclusion: The axonal degeneration rate is faster in RRMS patients in the first years of the disease than in later years. In addition, axonal degeneration occurs independently of inflammatory activity. Axonal degeneration is correlated with disability progression, but not with inflammatory findings, such as clinical episodes and MRI activity.
Now the visual pathway is affected early in MS and could account for this phenomenon…you know that is not the real point..Rest assurred more evidence is on the way. However we need evidence for the right therapeutics to use. As for correlations of R=0.04-0.5…as seen here….is meaning less.