#ThinkSpeak: unrelated comments as a forum for change

The best way to treat your pet troll is to be kind and patient; at Barts-MS we like to think that we are both kind and patient. #ThinkSpeak

Do you use, and read, unrelated comments? This is a useful feature of our blog that we added many years ago to improve our offering. It is important to let the blog evolve over time, which explains why we have expanded our readership over the years. The idea of the unrelated comments is to ask questions and start a conversation about a topic that is unrelated to a specific post. Yesterday one commentator asked a string of questions. I will try and answer these over the next few days. Three of the questions are all related to alemtuzumab.

Prof G do you claim alemtuzumab to be curative in MS? 

Incorrect. I have never claimed alemtuzumab is a cure for MS. I have always taken the position that based on the autoimmune hypothesis that PIRTs (pulsed immune reconstitution therapies) of which alemtuzumab is one may offer a potential cure. This is the underlying therapeutic principle that underpins PIRTs; in addition to alemtuzumab cladribine and HSCT can also be classified as PIRTs. I have also discussed many times what a potential cure would look like in MS and we are not there yet in terms of follow-up. I have always maintained that this is a 15-20 year experiment

Could something cure MS even though no-one knows why MS happens?

Yes, something could cure MS even if no-one knows why MS happens. This is called an empirical observation and it has happened many times in medicine, particularly in relation to environmental exposures. We didn't know how alcohol caused caused acute liver damage, but abstinence was the empirical cure. I don't agree with the comment that 'no-one knows why MS happens'. MS is a complex disease due to an interaction between genetic susceptibility and the environment. The main environmental factors are low vitamin D or low UV sun exposure, EBV and smoking. I am convinced that EBV is causal based on strong epidemiological data. We are working on a study design for an EBV vaccination study, that should answer the question whether or not  EBV is the cause of MS. What we don't know is how EBV triggers or drives MS once someone develops the disease. We have many ongoing research projects that are looking into this. We have discussed most of these projects on the blog under the 'Charcot Project' an initiative that brings all this research together. The Charcot Project is not one study but a many studies that look into the viral hypothesis of MS. 

Why do some patients who go onto alemtuzumab continue to progress?

This is has been discussed endlessly under the so called asynchronous progressive MS hypothesis and length-dependent axonopathy hypothesis. Unfortunately, progression is often primed by previous damage and switching off inflammation now with alemtuzumab is unable to repair the previous damage that has primed neurons and axons to die off over time. This is why we recommend early effective treatment to prevent damage. Another factor that plays out in so called 'progressive disease' is premature ageing. Life is a sexually-transmitted neurodegenerative disease. If we all live long-enough we will see the effects of ageing on the nervous system (poor memory, unsteadiness of gait, poor balance, reduced hearing, etc.). What protects us from age-related neurodegeneration is brain and cognitive reserve. Unfortunately, MS reduces both brain and cognitive reserve and brings ageing forward in time. Alemtuzumab like all other DMTs that have been licensed to treat MS have not been shown to impact on ageing of the nervous system. This is why some pwMS will continue to progress despite being rendered NEDA by alemtuzumab. Finally, the dreaded intrathecal plasma cell. One of the hypotheses that we are exploring is that the long-lived plasma cell, which makes immunoglobulin with the brain and spinal cord, may be responsible for delayed progression. We have shown that alemtuzumab does not impact on these cells and hence this is another reason why pwMS may continue to progress despite being treated with alemtuzumab. 

Our Pet Troll

I must point out that if this particular commentator had taken the time and effort to read the blog they would have had all their questions answered. This explains why we repeat ourselves. Most readers dip in and out of the blog and only read current posts, by repeating ourselves we hope the messages get through. We also need to curate the blog. Blogging software is not ideal for navigation. I have been working on creating a curation site with links to important posts to make it easier for you to find information and to help navigate the blog. This is part of evolving our site to make it more user-friendly; we really don't want the blog to be stuck in time. 

CoI: multiple