DE-FLAMES 2: Putting out the flames

Stopping the slow burn of progressive MS? The DE-FLAMES study. #MSBlog #MSResearch

"Thank you for responding so positively to yesterday's post; it clearly needs some more explanation."

"Why combination therapies? There are two ways MS damages and or kills nerve fibres and their processes or axons. The first is by cutting them as part of acute inflammation; the so called inflammatory scissors. The second is a delayed slow process that takes months to years to play out and is called the slow burn. We think inflammation damages nerves and axons and leaves them vulnerable to degenerate in the future. The inflammation also changes the environment in the nervous system that contributes to this slow burn. What we need to do is protect nerves from this slow burn and change the environment. To change the environment we need to switch of inflammation and ongoing autoimmune response that can attack new areas. This is why we need at the base of the pyramid an anti-inflammatory therapy. When then need to add on a drug to protect the damaged vulnerable nerves from dying in the hope that they can be repaired by natural repair mechanisms within the nervous system. The repair includes remyelination, regrowth of nerve processes and adaptation and plasticity of the brain. The latter is when 'normal areas' take-over, or help augment, the function of damaged areas. The brain and spinal cord has reserve or extra capacity to do this. This reserve capacity is not limitless and with time and increasing damage it runs out of capacity and progressive MS ensues. This is why we now know that progressive MS is not a process that starts late, it is there from the outset, hence the need for treating progressive disease throughout the course of the disease."

"What about primary progressive MS (PPMS)? We now know that PPMS and SPMS are the same disease and that PPMSers simply miss out on the relapsing phase of the disease. In my opinion they are unlucky, because relapses are a way of picking up MS earlier and treating it. By the time someone with PPMS presents they have run out of reserve capacity in at least one neurological system. I also beginning to realise that progressive MS affects different neurological systems at different rates. In other words reserve capacity may be exhausted in the motor system of the lower limbs first, but there is still reserve capacity in other systems that needs protecting, for example cognition or upper limb function. This is why the lessons learnt in relapse-onset disease are very relevant to people with PPMS. This is why Novartis, Roche and Teva are doing trials in PPMS; we are involved in all three of these programmes. I have therefore updated the slide to include the PPMS trials. You also need to realise that this slide is about MS@UCLP and is only a small fraction of the global activity that is occurring in the field of progressive MS, which includes both PPMS and SPMS." 

"The DE-FLAMES Trial above is looking at a putative neuroprotective agent, with a dual mode of action, that will added onto to a 1st-line DMT in RRMS. We want to target RRMS as this is where MSers have the most to gain. Our primary outcome will be a reduction in brain atrophy; brain atrophy is an integrator of end-organ damage and correlates with disease progression, reduced quality of life and cognitive impairment."

"The question we would like to ask you is if you had RRMS would you be willing to take and additional drug on top of an anti-inflammatory DMT to see if we can slow the progressive phase of MS? We know that 1st-line licensed DMTs are not effective at slowing down brain atrophy."

"The results of the survey below will be used in our grant application to get DE-FLAMES funded."

"I would like to point out that four of these neuroprotective investigator-led studies we have, or will be, embarking on come from research done as part of our PROMISE 2010 programme grant. I would therefore like to take this opportunity to thank the National MS Society of the US (NMSS) and MS Society of Great Britain and Northern Ireland for their generous and ongoing support; it is much appreciated and hopefully it will lead to a licensed treatment for progressive MS."

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