Barts-MS rose-tinted-odometer: ★★★★★
About 5 or 6 years ago, when we decided to replace the term DAF (disease-activity free) with NEDA (no evident disease activity) as a treatment target MS we created space to allow us to ‘move the goalposts’, i.e. to let our treatment targets in MS evolve as new insights and new technologies emerged.
This is particularly pertinent as the field now realises that MS is not relapses and MRI activity (Gd-enhancing and new T2 lesions), but other processes that underlie this. I refer to this as smouldering MS or the real MS. This is why we no have to develop treatments that slow or stop the accelerated end-organ damage that defines smouldering MS.
Please note that I say accelerated end-organ damage, because life in itself is a neurodegenerative disease. As part of the normal ageing process the end-organ (brain, spinal cord and periperipheral nervous system) gradually degenerate over time. Most people class ageing as a normal phenomenon, but it is clear that ageing is modifiable and that there are well-defined biological processes that drive ageing that can be targeted to slow down the inevitable decline associated with getting old. I think unhealthy ageing should be classified as a disease and treated as such.
So what can you do to slow down accelerated ageing? Most of the interventions at present relate to lifestyle interventions in particular diet and exercise. Which diet? I have discussed this previously and I think the scientific evidence supports caloric restriction, intermittent fasting and ketogenic diets as those most likely diets to modify ageing. Caloric restriction is not really feasible over a lifetime, which is why I promote intermittent fasting and ketogenic diets. The good news is that there are some preliminary trials that are looking into these diets in MS. I doubt these trials will be definitive, but they are likely to show that both intermittent fasting and ketogenic diets are at least safe in pwMS.
There is also emerging data that the pathways these diets activate can be activated by drugs, for example, by metformin and fumarates. There are ongoing studies and new trials planned of metformin in MS. As you know dimethyl fumarate and diroximel fumarate are licensed DMTs in MS. Both these DMTs are reasonably effective in MS and a proportion of patients are clearly super-responders to fumarates. I personally think we need to explore combination therapies with fumarates as one of the options in the combination to target smouldering MS. To be honest and pragmatic it is going to be a lot easier to test a cocktail of drugs in smouldering MS than a diet.
Other things you can do to tackle accelerated ageing is to prevent getting comorbities (diabetes, hypertension, etc.) or if you have them to make sure they are well controlled. To stop smoking, to consume alcohol in moderation, to improve your sleep hygiene, to reduce your anticholinergic medication load, to consider HRT (hormone replacement therapy), to prevent recurrent infections (chest, urinary tract, mouth, sinusesm etc.) and to make sure you don’t become socially isolated.
MS as a disease can have a dramatic impact on your social capital, i.e. the number of meaningful relationships you have. We now know that people with large social networks have better outcomes. Barts-MS have started investigating ways of helping our patients expand their social networks as a treatment strategy for MS.
Most of the messages in this blog post should not be new to you as I have written about all of them in the past, hence the links to other posts. However, it is good to repeat things and to remind you that a lot of what we are saying about the holistic management of MS, to improve long-term outcomes, is in your hands. This is why we self-management is so important.
Moving the Goalposts 2
As you may know after my recent accident I set myself a challenge, ‘Prof G’s crutches to 500 m Challenge’ to raise money for MS Research. However, I achieved this target yesterday (day 5 after discharge) so I also have had to move the goalposts. My new challenge is ‘Prof G’s bed to 5km Challenge’; I want to be able to walk 5km without stopping or using support before the 31st December. To achieve this I am hoping my pelvic and cervical spine fractures heal well and the pain subsides. Walking 650 meters yesterday was truly a mammoth challenge for me and I feel worse today (muscle stiffness and pain) than I did after running the virtual marathon last month. So please support me with my new 5km challenge to reach our funding target of £25,000. Please note that all of the money raised will go to Queen Mary University of London to support Dr Ruth Dobson and Dr Angray Kang’s COVID-19 MS Antibody Study. Their study is not only relevant to COVID-19, but will create the platform for remote testing of pwMS using blood spots. We are already planning a raft of other studies using this technology, but more on this later.