Prof G offers hope in that we can now go beyond simply no evident inflammatory disease activity as a treatment target and expect some disability improvement. Should this be the new aim of MS treatment
Reading this not only saddens me it frustrated the hell out if me and I then blame myself, have I made bad choices did I fully understand everything.
I feel that I had to decide on my medication rather than my doctor
recommending what they thought was right. Therefore if I did take DMD or didn’t it wouldn’t make much difference.
Only offered DMD after a couple of relapses. Before that they thought at NHNN that it was an isolated incident.
Was offered a betaferon only which I did not want to take as research was showing it was pretty ineffectual and bad side effects. Asked if I could go on Alemtuzumab only to be told no you have to fail at two other drugs before you get this.
I waited for a pill rather than an injection that would only reduce my relapses my 1/3 as I’d only had a couple of relapses. I took Tecfidera when it became available at the NHNN. I was one of the first patients.
After falling and starting to use a stick for about nine months and after maybe a year of being on Tecfidera I was offered Alemtuzumab.
That was almost 5 years ago. Wish I had been given this drug many years earlier as you are recommending now. My foot drop is so bad I cannot walk very far at all although I use crutches and massively impacted my life.
Also Physiotherapy I felt only concentrated on what I could not do rather that what I could. A neurologist also said Physiotherapy wouldn’t really help my MS.
How frightened do you think I feel now. How much bad information do I feel I received. No guidance I feel at the stat of my MS diagnosis. Just left up to me. Go on drugs or not.
Thank you for this very informative article. I was diagnosed with RRMS in 2016 (after 11 years of symptoms including chronic pain) and was not really given any guidance in regards to medication, just provided with a handful of brochures and told "Let me know if you have any questions." So no discussion of NEIDA. I had no idea there were such things as infusions; I thought it was either jab myself every day or take an oral medication so I chose Gilenya. Having said that, it has worked well for me and I am very grateful. I am also following the Overcoming MS program which is a whole healthy lifestyle choice and not just a diet, and my strength continues to measurably improve. Making sure I exercise and meditate (both part of the OMS program) has made a huge difference in my symptoms.
Great article! I was diagnosed in 2016 and put immediately on to natalizumab. No new lesions, no relapses, but my mobility has got steadily worse. I was offered lemtrada as a DMT option initially but was very much left to make my own mind up, and most of the research I read focused on natalizumab being more effective for reducing relapses. No information about the potential for disability improvement. At the time of diagnosis I didn't have any noticeable disability, so it didn't cross my mind to ask. Agree with the other poster & Prof G that exercise is great for staving off disability. Unfortunately I fell off my new ebike a few weeks ago & broke my wrist!! 😫 Be careful!
I was diagnosed in 2007. The only treatment I was offered was betaferon. I moved from that to Avon ex and then Helena when it became available. Finally alemtuzamab was approved in Australia and I was treated with this in 2015-16. I am 53. Although I have meds my disability is increasing (I just went shopping for a wheelchair) I have to say that I find your advice to treat eArly extremely frustrating as in reality pwMS usually have very limited options. We can o ly make choose from the options we are offered by our neurologist. I wish you guys would get yourselves on the same page so that our outcomes don’t depend so much on which neurologist we see.
Jane, I'm sorry to hear about you getting worse. You are correct it is all about timing. You have to give these treatments early before MS changes its spots to derive the benefits of disability improvement. Once the processes that drive smouldering MS are established they don't respond to anti-inflammatory treatments. This is why we need add-on combination therapies to tackle smouldering MS.
Hi Prof G. Thanks for this great article. I was not told about disability improvement but happily had alemtuzumab in 2015/16 and have improved physically and cognitively.
Thank you. My patients who have been treated early with alemtuzumab are streets ahead f the other cohorts of patients I have under my care when it comes to long-term outcomes. It is a great pity the MS community haven't adopted this treatment strategy more widely.
Yes indeed. I remember being shocked when my MS nurse commented that they had moved on to ocrelizumab like it was the latest innovation. It was on the tip of my tongue to say that it is less effective. I guess I got diagnosed at the right time, when alemtuzumab was in vogue!
Dear Prof G, thank you very much for this great article.
Never did my neuros talk to me about disability improvement, they are all like 'lets watch what happens' (am not on a high efficacy DMT, to be honest at the moment I don't know what I'm talking because I'm in a study, I will know in about week or so) even though I have active RRMS (visible on MRI and in relapses, went from 2.0 to 4.0 EDSS in one year), it is so sad. Now that I'm learning and reading more and more about MS, I am getting more proactive, wanting needed imunisations ASAP, and it makes me sad, because it feels like I'm not understood in my MS centre, and I feel like I'm losing time. But, let's not lose hope and effort, after all, it is my life, I have to take care of myself the best way I can.
Thank you. I've just been offered treatment for the first time though I have deteriorated slowly but surely since my diagnosis in 2013 . I'm having a relapse that showed on mri. I've been offered Siponimod. I really hope this will help me. I have not been told of improvement just slowing down of the disease . Walking/trekking was my great joy, now I cycle.
I started cycling last year to avoid public transport during the pandemic. I was always too scared to cycle before but then something even more scary came along and tipped the balance I guess! Now I'm in this cycling world I'm discovering so much, including the number of people who use a bicycle as a mobility aid. I've just finished reading the Equalities Impact Assessment for a Low Traffic Neighborhood my council wants to introduce which had some great info and made me feel seen!
I can't help thinking that physical activity is in itself a way to improve disability. The more we move the more we can. I also have EDS and it got so bad once that I couldn't walk very far at all and would take the bus one or two stops because I couldn't walk that far. Physiotherapy got me on the right track and I can now run, something I thought I could never do.
Yes, I have written about exercise and neurorehabilitation before being the most under-prescribed DMT at our disposal. Exercise, both physical and mental, stimulates recovery of function. If you don't use it you lose it.
I also haven't seen my neurologist for 2 years. ...the offer of treatment has been done by letter. I live in an area with a real shortage of consultants.
This is purely informative and perhaps something or another is in this for someone. I try to answer the question too. My only DMT (about) has been Interferon 1B, the first disease modifier which came out circa 1994-5. There were no choices; nothing for anyone to decide. Kind of like, “do it or die”. And yes, they recommended early treatment with this, back then. Many did not listen. I know many think it is a real “nothing”, but not at all for me, and I’ve had my wheel chair in mothballs since ’97 or ’98. I am one of those who look on the outside, to have improved, and I certainly have from the low points, and it is all Betaseron and perhaps other things I’ve done on my own. Doctors didn’t know what to advise as this point, if you were on Betaseron. We all hoped it would end MS. Lots of us improved. But the evidence for “no cure” came out later (I had stopped following things at that time. I was too busy!).
I always believed that if the constant attacks and relapses stopped, some stuff would come back naturally and other things couylkd be re-learned. My doctors agreed, some had a suggestion or two, one helped with a law suit, another with SSI, and I learned to use what was out there while being fully aware that some (most), didn’t need to know. I confide more now, at an older age, as it seems people are more willing to give their respect. Maybe that’s me, too. I knew then, things were not as they once had been, and my direction(s) changed slowly over time. Otherwise I’d still just be banging my head against the wall (and I know how to do that well).
So one lesson in all of this, is that most things are relative. I am now 63. “Major” issues are bladder control, some fatigue, less accuracy when presented with a host of things all at once, and walking (after 25 years of a minor gait change after a remitted major relapse, my natural flat foot has collapsed all the way (ouch!). Smoldering? My doc and I don’t think so. But I continue and know things could be much, much worse.
1989 I had numbness on my face. 1991 I had double vision and was told in all likelihood, given a spot or two on an x-ray, that I had MS. At The U of Illinois at the time working on a PhD, the only sources of info were at or through the library. At an internship, I had slurred speech combined with stumbling. Optic nutritious. Optic Nutritious again and more stumbling, Everything had remitted thus far. My first “forever job” met with total resistance to the idea I had MS, after more stumbling and double vision and wearing a patch. Started Betaseron. Law suit. Most women not interested in a guy with MS. Teaching college (not as easy as before). Married (still, happily), bankruptcy, SSI disability, real estate purchase with proceeds of law suite, rental income too, moved out to the country and enjoy my life and what I can do. It’s a life with MS as a major turning point, but it is myself who suffered the consequences and navigated the way through. I had to make my own path.
I did best with most MS expert neurologists and the head of an Academic Dept. Regular neurologists, not so much. One “expert” switched me to Avonex and I relapsed, 1st time in years. That was 2001. On my own I insisted back on Betaseron (a stronger interferon). Mr. Avonex wanted to switch me to a new DMT, the one that could give you a brain disease. Later, I would learn he was called “Mr. Avonex”. Other, regular neurologists, early on, really had no helpful insight. One expert said, when I was new to him, but after years of NEDA, “if it’s not broken don’t fix it”. So I stayed on Betaseron till 2018, did a year’s stint on Ocrevus, and then the Pandemic persuaded me early on to rehab my immune system, so I stopped. Tried Biotin…nothing. Vitamin D because I am naturally low. Simvastatin for cholesterol (which is good), at ½ the MS experimental dose. Still looking for that miracle or another useful add-on, but I’m quite happy where I am now. No detectable changes, other than the bladder and leg. Bladder managed with men’s “diaper”, leg with a walking stick sometimes, when outside. I might do probiotics (Visbiome), still reading up. Swank diet, sometimes more ridged than other times, since probable diagnosis (that was the only thing out there, other than BEE STINGS (REALLY!)).
My salvation? PERHAPS ? -being flexible and adaptive, being uncompromising too in the right place. If I had to do it again with today’s meds? Reconstitution and then hunkering down for a bit to protect myself from the covid ogres. Then total freedom! (maybe).
After 2 years on cladribine, I was NEDA according to my most recent MRI. On MRI it stated my C7 lesion was looking “less suspicious” too. 👍 However I would consider myself NEDADI. Since starting cladribine I have improved significantly. I really hope that we can start to talk about NEDADI… gives me so much hope…. I don’t just want maintenance.
“In our centre we don’t accept this as a fait accompli, we now offer patients a lumbar puncture to see if they have raised neurofilament levels in their spinal fluid, which is a biochemical marker of ongoing inflammatory disease activity.” What do raised neurofilament levels in the spinal fluid indicate? Is the damage the result of smouldering MS or damage from focal inflammation coming from outside the CNS? What can your centre offer a patient with inactive progressive MS? I thought there were no licensed therapies?
No licensed treatments, which is why we are doing trials. Cladriplus, Sizomus and Chariot-MS. This is the cohort of patients we have offered off-label subcutaneous cladribine to in the past and based on insights from this cohort we have designed our other studies.
I have had MS for 15.5 years. I was on Betaferon a year after the first symptoms appeared and then Rebif for a year and despite that, I relapsed quarterly for the first 3 years. After starting Tysabri I had no relapses although after 8 years on it I could feel the progression of symptoms from before I stared it. I then finished Lemtrada in Jan 2019 and after R1 I could feel the progression lessening but it had worsened in the 4 month washout period between Tysabri and starting Lemtrada. After R2 it has stabilised completely and, although I don't know if I will get worse, if I stay like this then I can cope with staying as I am. That said I have notice little improvements here and there such as the neuromuscular fatigue has lessened, especially in left hand although it is still just as bad as it I was in my right hand which is my dominant one. As for the relapses, I have not one in over 12.5 years and I am hoping that Lemtrada will certainly keep it that way.
Not all but many. It's because of age, comorbidities and disability. The older you are and the more disabled you are and the more comorbidities you have the harder it is to show a treatment effect.
Very soon. The assay is now been validated on the Siemens diagnostic platform and hence will become widely available. Please note it is not only useful in MS but other disease areas as well.
Dear Prof. G. if you talk about disability improvement, how is this defined/measured?
[e.g. When patient A's fatigue improves, their overall fitness might improve, leading to major perceived improvements. On the other hand, when patient B's EDSS drops a point, but he gets more fatigued, he might actually feel worse. I fear that MS-researchers would say patient B improved, but patient A remained stable...]
No, I was not told about improvement. I was on Avonex for 15 years before an acquaintance told me about HSCT. By the time I did it I was EDSS 6.5 and I fear too late for it to have been successful. I’m now EDSS 7 and despite physio three times a week, probably because of a desk job, am less able, more stiff, less mobile than ever before… I’m also on no DMDs. Is there hope for improvement now or is too late?
Diagnosed in 2008.
Reading this not only saddens me it frustrated the hell out if me and I then blame myself, have I made bad choices did I fully understand everything.
I feel that I had to decide on my medication rather than my doctor
recommending what they thought was right. Therefore if I did take DMD or didn’t it wouldn’t make much difference.
Only offered DMD after a couple of relapses. Before that they thought at NHNN that it was an isolated incident.
Was offered a betaferon only which I did not want to take as research was showing it was pretty ineffectual and bad side effects. Asked if I could go on Alemtuzumab only to be told no you have to fail at two other drugs before you get this.
I waited for a pill rather than an injection that would only reduce my relapses my 1/3 as I’d only had a couple of relapses. I took Tecfidera when it became available at the NHNN. I was one of the first patients.
After falling and starting to use a stick for about nine months and after maybe a year of being on Tecfidera I was offered Alemtuzumab.
That was almost 5 years ago. Wish I had been given this drug many years earlier as you are recommending now. My foot drop is so bad I cannot walk very far at all although I use crutches and massively impacted my life.
Also Physiotherapy I felt only concentrated on what I could not do rather that what I could. A neurologist also said Physiotherapy wouldn’t really help my MS.
How frightened do you think I feel now. How much bad information do I feel I received. No guidance I feel at the stat of my MS diagnosis. Just left up to me. Go on drugs or not.
Thank you for this very informative article. I was diagnosed with RRMS in 2016 (after 11 years of symptoms including chronic pain) and was not really given any guidance in regards to medication, just provided with a handful of brochures and told "Let me know if you have any questions." So no discussion of NEIDA. I had no idea there were such things as infusions; I thought it was either jab myself every day or take an oral medication so I chose Gilenya. Having said that, it has worked well for me and I am very grateful. I am also following the Overcoming MS program which is a whole healthy lifestyle choice and not just a diet, and my strength continues to measurably improve. Making sure I exercise and meditate (both part of the OMS program) has made a huge difference in my symptoms.
Great article! I was diagnosed in 2016 and put immediately on to natalizumab. No new lesions, no relapses, but my mobility has got steadily worse. I was offered lemtrada as a DMT option initially but was very much left to make my own mind up, and most of the research I read focused on natalizumab being more effective for reducing relapses. No information about the potential for disability improvement. At the time of diagnosis I didn't have any noticeable disability, so it didn't cross my mind to ask. Agree with the other poster & Prof G that exercise is great for staving off disability. Unfortunately I fell off my new ebike a few weeks ago & broke my wrist!! 😫 Be careful!
I was diagnosed in 2007. The only treatment I was offered was betaferon. I moved from that to Avon ex and then Helena when it became available. Finally alemtuzamab was approved in Australia and I was treated with this in 2015-16. I am 53. Although I have meds my disability is increasing (I just went shopping for a wheelchair) I have to say that I find your advice to treat eArly extremely frustrating as in reality pwMS usually have very limited options. We can o ly make choose from the options we are offered by our neurologist. I wish you guys would get yourselves on the same page so that our outcomes don’t depend so much on which neurologist we see.
Jane, I'm sorry to hear about you getting worse. You are correct it is all about timing. You have to give these treatments early before MS changes its spots to derive the benefits of disability improvement. Once the processes that drive smouldering MS are established they don't respond to anti-inflammatory treatments. This is why we need add-on combination therapies to tackle smouldering MS.
Hi Prof G. Thanks for this great article. I was not told about disability improvement but happily had alemtuzumab in 2015/16 and have improved physically and cognitively.
Thank you. My patients who have been treated early with alemtuzumab are streets ahead f the other cohorts of patients I have under my care when it comes to long-term outcomes. It is a great pity the MS community haven't adopted this treatment strategy more widely.
Yes indeed. I remember being shocked when my MS nurse commented that they had moved on to ocrelizumab like it was the latest innovation. It was on the tip of my tongue to say that it is less effective. I guess I got diagnosed at the right time, when alemtuzumab was in vogue!
Dear Prof G, thank you very much for this great article.
Never did my neuros talk to me about disability improvement, they are all like 'lets watch what happens' (am not on a high efficacy DMT, to be honest at the moment I don't know what I'm talking because I'm in a study, I will know in about week or so) even though I have active RRMS (visible on MRI and in relapses, went from 2.0 to 4.0 EDSS in one year), it is so sad. Now that I'm learning and reading more and more about MS, I am getting more proactive, wanting needed imunisations ASAP, and it makes me sad, because it feels like I'm not understood in my MS centre, and I feel like I'm losing time. But, let's not lose hope and effort, after all, it is my life, I have to take care of myself the best way I can.
Thank you. I've just been offered treatment for the first time though I have deteriorated slowly but surely since my diagnosis in 2013 . I'm having a relapse that showed on mri. I've been offered Siponimod. I really hope this will help me. I have not been told of improvement just slowing down of the disease . Walking/trekking was my great joy, now I cycle.
I started cycling last year to avoid public transport during the pandemic. I was always too scared to cycle before but then something even more scary came along and tipped the balance I guess! Now I'm in this cycling world I'm discovering so much, including the number of people who use a bicycle as a mobility aid. I've just finished reading the Equalities Impact Assessment for a Low Traffic Neighborhood my council wants to introduce which had some great info and made me feel seen!
I can't help thinking that physical activity is in itself a way to improve disability. The more we move the more we can. I also have EDS and it got so bad once that I couldn't walk very far at all and would take the bus one or two stops because I couldn't walk that far. Physiotherapy got me on the right track and I can now run, something I thought I could never do.
Yes, I have written about exercise and neurorehabilitation before being the most under-prescribed DMT at our disposal. Exercise, both physical and mental, stimulates recovery of function. If you don't use it you lose it.
Sounds like you should have been treated earlier. Siponimod is licensed in the UK and the EU for active SPMS.
I also haven't seen my neurologist for 2 years. ...the offer of treatment has been done by letter. I live in an area with a real shortage of consultants.
This makes me very sad...every time I asked I was told there wasn't anything for me. I even asked for a second opinion and was told the same.
This is purely informative and perhaps something or another is in this for someone. I try to answer the question too. My only DMT (about) has been Interferon 1B, the first disease modifier which came out circa 1994-5. There were no choices; nothing for anyone to decide. Kind of like, “do it or die”. And yes, they recommended early treatment with this, back then. Many did not listen. I know many think it is a real “nothing”, but not at all for me, and I’ve had my wheel chair in mothballs since ’97 or ’98. I am one of those who look on the outside, to have improved, and I certainly have from the low points, and it is all Betaseron and perhaps other things I’ve done on my own. Doctors didn’t know what to advise as this point, if you were on Betaseron. We all hoped it would end MS. Lots of us improved. But the evidence for “no cure” came out later (I had stopped following things at that time. I was too busy!).
I always believed that if the constant attacks and relapses stopped, some stuff would come back naturally and other things couylkd be re-learned. My doctors agreed, some had a suggestion or two, one helped with a law suit, another with SSI, and I learned to use what was out there while being fully aware that some (most), didn’t need to know. I confide more now, at an older age, as it seems people are more willing to give their respect. Maybe that’s me, too. I knew then, things were not as they once had been, and my direction(s) changed slowly over time. Otherwise I’d still just be banging my head against the wall (and I know how to do that well).
So one lesson in all of this, is that most things are relative. I am now 63. “Major” issues are bladder control, some fatigue, less accuracy when presented with a host of things all at once, and walking (after 25 years of a minor gait change after a remitted major relapse, my natural flat foot has collapsed all the way (ouch!). Smoldering? My doc and I don’t think so. But I continue and know things could be much, much worse.
1989 I had numbness on my face. 1991 I had double vision and was told in all likelihood, given a spot or two on an x-ray, that I had MS. At The U of Illinois at the time working on a PhD, the only sources of info were at or through the library. At an internship, I had slurred speech combined with stumbling. Optic nutritious. Optic Nutritious again and more stumbling, Everything had remitted thus far. My first “forever job” met with total resistance to the idea I had MS, after more stumbling and double vision and wearing a patch. Started Betaseron. Law suit. Most women not interested in a guy with MS. Teaching college (not as easy as before). Married (still, happily), bankruptcy, SSI disability, real estate purchase with proceeds of law suite, rental income too, moved out to the country and enjoy my life and what I can do. It’s a life with MS as a major turning point, but it is myself who suffered the consequences and navigated the way through. I had to make my own path.
I did best with most MS expert neurologists and the head of an Academic Dept. Regular neurologists, not so much. One “expert” switched me to Avonex and I relapsed, 1st time in years. That was 2001. On my own I insisted back on Betaseron (a stronger interferon). Mr. Avonex wanted to switch me to a new DMT, the one that could give you a brain disease. Later, I would learn he was called “Mr. Avonex”. Other, regular neurologists, early on, really had no helpful insight. One expert said, when I was new to him, but after years of NEDA, “if it’s not broken don’t fix it”. So I stayed on Betaseron till 2018, did a year’s stint on Ocrevus, and then the Pandemic persuaded me early on to rehab my immune system, so I stopped. Tried Biotin…nothing. Vitamin D because I am naturally low. Simvastatin for cholesterol (which is good), at ½ the MS experimental dose. Still looking for that miracle or another useful add-on, but I’m quite happy where I am now. No detectable changes, other than the bladder and leg. Bladder managed with men’s “diaper”, leg with a walking stick sometimes, when outside. I might do probiotics (Visbiome), still reading up. Swank diet, sometimes more ridged than other times, since probable diagnosis (that was the only thing out there, other than BEE STINGS (REALLY!)).
My salvation? PERHAPS ? -being flexible and adaptive, being uncompromising too in the right place. If I had to do it again with today’s meds? Reconstitution and then hunkering down for a bit to protect myself from the covid ogres. Then total freedom! (maybe).
Great read, thank you 👏👏👏
After 2 years on cladribine, I was NEDA according to my most recent MRI. On MRI it stated my C7 lesion was looking “less suspicious” too. 👍 However I would consider myself NEDADI. Since starting cladribine I have improved significantly. I really hope that we can start to talk about NEDADI… gives me so much hope…. I don’t just want maintenance.
Super read. Thank you.
“In our centre we don’t accept this as a fait accompli, we now offer patients a lumbar puncture to see if they have raised neurofilament levels in their spinal fluid, which is a biochemical marker of ongoing inflammatory disease activity.” What do raised neurofilament levels in the spinal fluid indicate? Is the damage the result of smouldering MS or damage from focal inflammation coming from outside the CNS? What can your centre offer a patient with inactive progressive MS? I thought there were no licensed therapies?
No licensed treatments, which is why we are doing trials. Cladriplus, Sizomus and Chariot-MS. This is the cohort of patients we have offered off-label subcutaneous cladribine to in the past and based on insights from this cohort we have designed our other studies.
I have had MS for 15.5 years. I was on Betaferon a year after the first symptoms appeared and then Rebif for a year and despite that, I relapsed quarterly for the first 3 years. After starting Tysabri I had no relapses although after 8 years on it I could feel the progression of symptoms from before I stared it. I then finished Lemtrada in Jan 2019 and after R1 I could feel the progression lessening but it had worsened in the 4 month washout period between Tysabri and starting Lemtrada. After R2 it has stabilised completely and, although I don't know if I will get worse, if I stay like this then I can cope with staying as I am. That said I have notice little improvements here and there such as the neuromuscular fatigue has lessened, especially in left hand although it is still just as bad as it I was in my right hand which is my dominant one. As for the relapses, I have not one in over 12.5 years and I am hoping that Lemtrada will certainly keep it that way.
Why is it that almost every research study excludes people who have had MS for a long time (20+ years)?
Not all but many. It's because of age, comorbidities and disability. The older you are and the more disabled you are and the more comorbidities you have the harder it is to show a treatment effect.
I just want the deterioration to stop so my body can have a chance to heal and possibly improve.
“when the assay to measure neurofilament in peripheral blood becomes available for general use” Approximately when is this assay expected?
Very soon. The assay is now been validated on the Siemens diagnostic platform and hence will become widely available. Please note it is not only useful in MS but other disease areas as well.
Dear Prof. G. if you talk about disability improvement, how is this defined/measured?
[e.g. When patient A's fatigue improves, their overall fitness might improve, leading to major perceived improvements. On the other hand, when patient B's EDSS drops a point, but he gets more fatigued, he might actually feel worse. I fear that MS-researchers would say patient B improved, but patient A remained stable...]
In trials, disease improvement is based on EDSS improvement that is not linked with fatigue.
That's what I thought. Does that make any sense in your opinion?
No, I was not told about improvement. I was on Avonex for 15 years before an acquaintance told me about HSCT. By the time I did it I was EDSS 6.5 and I fear too late for it to have been successful. I’m now EDSS 7 and despite physio three times a week, probably because of a desk job, am less able, more stiff, less mobile than ever before… I’m also on no DMDs. Is there hope for improvement now or is too late?