CategoryLab Lessons

Alemtuzumab and B cells. Snooze and you may lose

About 5 or more years ago Prof G and I went to see Genzyme to propose a study on doing B cell depletion after alemtuzumab to try and limit, ideally prevent, secondary autooimmunity that occurred in about 50% of people with MS who were treated with MS. At the time there was no ocrelizumab, cladribine in the picture and they simply were not interested in B cells. They thought T regs increased after...

Imaging astrocytes

18F-THK5351 PET Can Identify Astrogliosis in Multiple Sclerosis Plaques. Ishibashi K, Miura Y, Hirata K, Toyohara J, Ishii K. Clin Nucl Med. 2019 Jul 24. doi: 10.1097/RLU.0000000000002751.  A 26-year-old woman with relapsing-remitting multiple sclerosis (MS) underwent F-THK5351 PET during a remission period. PET imaging showed that small regions with elevated uptake of F-THK5351 were scattered in...

HSCT in MS, more a remission than a cure

In a prose to seduce the weary palate, the British neurologist, I recollect saying: “What should be the aims of HSCT treatment? At worst, remission. At best, a cure“. I may just have to eat my words… In a small study from Uppsala University (n=45), Larsson et al. report the effects of HSCT on neuronal damage (using neurofilament levels) and inflammation (IgG index and...

OXO Study

We want to build a sandwich to tackle the many facets of multiple sclerosis that result in neuroaxonal loss. At the base of treatment pyramid, we need an anti-inflammatory onto which we want to add a neuroprotectant, i.e. the combination therapy strategy. You need to protect damaged and vulnerable axons so that you can then remyelinate them or restore their function. We assume this makes sense...

I’m wrong…it’s all T cells

A new study finds a another T cell subtype for MS This time the cell expresses Granulocycte macrophage growth factor and a chemokine recepter called CXCR4. There is a relatively new detection system and they have looked in the MS brain and found this one. Yes yes its T cells, It’s T cells I give up. They found a CD4 T cell is that surprising? So off we go and do a new set of EAE studies...

ARRIVE- REVERSE & ARRIVE AGAIN. Animal Experiments

The ARRIVE guidelines are a set of reporting suggestions for reporting animal work. These follow on from the CONSORT guidelines about reporting clinical trials in humans. The aim was to improve the transparency of animal studies to help them be more reproducible and translatable. According to the authors the ARRIVE 2010 have not been fully adopted, will the 2019 revision improve this? I suspect...

#ThinkCognition

If you have MS-related cognitive impairment would you want a treatment to improve your cognitive function?  The study below shows that dalfampridine, or fampridine, improves cognition in particular processing speed in MSers with cognitive impairment. Importantly the improvement on the SDMT (Symbol Digit Modalities Test) was greater than 4 points, which is considered clinically meaningful in that...

Is too much vitaminD bad for you?

I noticed DrK tweeted on this and suggested that I have a look. The implications are that a middling amount is beneficial, but too much vitamin D is bad for you because it affects calcium levels in T cells. This may be lapped-up, because no doctors would think that you should be eating vitamin D capsules like smarties (Sugar coated chocolate sweets). Of course one says No s**t Sherlock, we...

Inactive MS; does it exist?

I had an interesting discussion with some like-minded colleagues recently about active and inactive MS. We seemed to agree on what active MS is, be it in the relapsing or progressive phases of MS. However, we couldn’t really agree on what inactive MS is. Take this following case scenario; many said he was inactive, but others felt he had active MS and should have his treatment switched. Would you...

Goalposts

We need to keep pushing the envelope and moving the goalposts in terms of our treatment targets in MS.  As MS advances innate immune activation with microglial and astrocyte activation occurs. However, the latter may be adaptive in response to damage and hence a good thing, which is why I am sceptical about treatments aimed at targeting these cells in advanced MS.  In comparison, B-cells and...

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