Why don’t potent anti-inflammatory DMTs switch off worsening of disability? They do, but the extent to which they do depends on how much pre-existing damage there is in a particular pathway. The more damage that accumulates, the fewer healthy neurons and axons there are to repair the pathway, the less likely that pathway will flat-line or improve. In all likelihood disability continues to worsen because of the amount of inflammatory damage accumulated in the past. This is why there is therapeutic lag, i.e. you will only see slowing down of worsening, or flat-lining, occurring in the future once the delayed neuronal and axonal loss has run its course. The timing is length-dependent, in other words the longer the axon the more vulnerable it is to multiple hits and because of its metabolic load it degenerates first. This is why we see the ‘clinically-apparent’ progressive phase of MS start in the bladder and legs and only much later it involves the arms and hands and then later speech and swallowing. These observations underpin our #ThinkHand campaign to make the MS community focus on trying to preserve hand and arm function in people with more advanced MS.
The other issue that needs to be kept in mind is that premature ageing may underlie some of the delayed worsening of disability we see in pwMS. Reserve capacity protects us from age-related neurodegeneration, which is a fact of life. Speak to anyone older than 50 and they are acutely aware of their nervous system beginning to fail; reduced memory, slower reflexes, poor balance, etc. If you shred your reserve, which is what MS does, then the ageing curve is shifted left and age-related worsening of disability starts much earlier. Unfortunately, we don’t have any anti-ageing drugs at present, except for well-known lifestyle factors and preventing, or treating, so called comorbidities (other diseases) that accelerate ageing.
The following are some of the slides that I presented at the Roche satellite symposium at the EAN 2017 in Amsterdam. The purpose of the presentation was to get these concepts across. I hope the slides are self explanatory? If not, I would be willing to do a webinar (Google Hangout) to explain them and to answer any of your questions.
If you buy into the above concepts then we need your support to make the widerMS community aware that in all likelihood ocrelizumab will not be made available to treat PPMS under the NHS and therefore access to the drug will be inequitable. The latter is a serious problem, undermining the founding principles f socialist healthcare and makes me very angry.