Where you hoping for a blood neurofilament level to tell your neurologist that your MS is stable or getting worse, i.e. as a guide to help with treatment decisions? It is not that simple.
“SARS-CoV-2 can induce HERV-W ENV [which as been linked to MS, if I understand correctly] expression in cells from individuals with symptomatic and severe COVID-19. Rightwards arrow Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID.”
Yes, I am aware of this data and it potentially provides an alternative treatment strategy. I am not sure if you are aware that EBV is one of the most potent transactivators of HERVs.
I am 56 female with SPMS. My disability has increased steadily over the past four years.
(probably have an EDSS of 6.5). I have been on Filgolimod since 2010. I was on beta interferon injections from 2005 to 2010).
My neurologist feels the Filgolimod is working as I have no new detectable lesions. He won’t consider any other treatment. My last MRI was 2020.
I need a future with options.
I am looking at HSCT. I’ve been told I won’t qualify for that on the NHS. What’s your view.? I do many alternative therapies such as massage diet exercise meditation et cetera. What are the medical options to consider?
Mary-Ann your story is so familiar in that you are NEIDA (no evident inflammatory disease activity), but are getting worse. We call this smouldering MS. At the moment we don't have any licensed treatments for smouldering disease. I assume you have read the other case studies n the MS-Selfie site about patients like you? Simply enter 'smouldering' into the search function.
Thank you for sharing this post in relation to my questions about SPMS and AHSCT.
A number of questions arise:
1a) how do I find out about participating in the MS society drug trial mentioned in your post? When are results expected?
1b) Are there any level three drugs you would suggest I consider using and move off Fiilgolimod?
2) I understand AHSCT is not an option on the NHS. However, is it medically possible as a private procedure? (I have a child undergoing treatment for childhood leukaemia -ALL. I have lived with the infection risk and low or negative neutrophil counts for over a year. It would not be a big consideration should I have the AHSCT treatments.
3). My EDSS score is based on an online self completed questionnaire.
It seems that 6.5 is the upper level of a score permitting AHSCT. Why else would you consider my estimated score as a factor excluding me from the AHSCT option?
I posted my questions/circumstances yesterday and your response was most interesting. I hope you’re able to reference the post and your reply.
Thanks for the work you do with MS Selfie. It’s a wonderful source for people like me with MS and my family.
1a) how do I find out about participating in the MS society drug trial mentioned in your post? When are results expected?
The trial has not started yet and is due to start later this year. You can watch their website. I will also notify you via this site.
1b) Are there any level three drugs you would suggest I consider using and move off Fingolimod?
In patients with SPMS we may consider siponimod based on it having CNS effects. In subjects not labelled as having SPMS we would do a lumbar puncture and check CSF NFL levels and if raised we would consider subcutaneous cladribine.
2) I understand AHSCT is not an option on the NHS. However, is it medically possible as a private procedure? (I have a child undergoing treatment for childhood leukaemia -ALL. I have lived with the infection risk and low or negative neutrophil counts for over a year. It would not be a big consideration should I have the AHSCT treatments.
Yes, there are private units that would do it almost all-comers, but the risks go up the older you are and the more disabled you are. This is why the London AHSCT set disability cutoffs.
3). My EDSS score is based on an online self completed questionnaire.
EDSS 6.0 is one stick and you have to walk 100 m non-stop. EDSS 6.5 is two sticks to walk 10 m non-stop.
Based on your explanation, I think my EDSS is definitely a six. It may even be a 5.5 as I can walk 10m unassisted non stop. It’s the right and tremors that are a real nuisance.
With smoldering MS would the use of DMT’s slow the progression of the disease. As reference to the following -
‘Whereas smouldering MS refers to both PIRA and other markers of ongoing end-organ damage, such as progressive brain volume loss, grey matter loss, thalamic atrophy, slowly expanding lesions, raised CSF neurofilament levels, cognitive decline, retinal nerve fibre layer thinning, worsening neurological function using neurological stress tests (walking distance, running speed, hand-eye coordination, balance tests, hand-eye coordination, .... ) and other emerging clinical outcome measures and imaging biomarkers. It is important to realise that you can have a stable EDSS (no PIRA) and you can still be getting worse from smouldering MS. This is why I prefer the term smouldering MS to PIRA and don’t refer to them as synonyms. Smouldering MS is so much more than PIRA’.
Relating to progressive brain volume loss, cognitive decline, grey matter loss et. al the other areas you mentioned? Would DMT’s slow these ares of progression of the disease?
Yes, in that DMTs we think anti-inflammatory DMTs stop new lesion formation and hence reduce the rate smouldering pathology accumulates. However, DMTs don't really affect preexisting smouldering lesions and hence don't stop the worsening that inevitably happens.
I suggest you read the following Newsletter that explains these processes:
Dr. G: Given the fact that HERV transactivates EBV, have you noticed any incidental improvement in fatigue in any people with MS taking the new Pfizer drug?
When I was Dx'd, they did a spinal tap and drew some CSF.. At the time the doctor told me it was negative for any proteins or filaments.. I had over 100 lesions at that time in my brain but nothing in my cord yet. I am wondering why the spinal fluid would be clear?
Prof G, may I ask what information is derived from NFH results? I read that they are supposed to signify axon loss, not myelin. I have lambda, not kappa paraproteins.
NB. I had to listen three times as your voice is so beautifully soporific that I dozed off...You should record meditation cd's.
Thank you for this post.
This is on a separate subject, but do you have any thoughts about the relevance of this article for pwMS?
https://www.medrxiv.org/content/10.1101/2022.01.18.21266111v2
“SARS-CoV-2 can induce HERV-W ENV [which as been linked to MS, if I understand correctly] expression in cells from individuals with symptomatic and severe COVID-19. Rightwards arrow Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID.”
Yes, I am aware of this data and it potentially provides an alternative treatment strategy. I am not sure if you are aware that EBV is one of the most potent transactivators of HERVs.
I am 56 female with SPMS. My disability has increased steadily over the past four years.
(probably have an EDSS of 6.5). I have been on Filgolimod since 2010. I was on beta interferon injections from 2005 to 2010).
My neurologist feels the Filgolimod is working as I have no new detectable lesions. He won’t consider any other treatment. My last MRI was 2020.
I need a future with options.
I am looking at HSCT. I’ve been told I won’t qualify for that on the NHS. What’s your view.? I do many alternative therapies such as massage diet exercise meditation et cetera. What are the medical options to consider?
Mary-Ann
Mary-Ann your story is so familiar in that you are NEIDA (no evident inflammatory disease activity), but are getting worse. We call this smouldering MS. At the moment we don't have any licensed treatments for smouldering disease. I assume you have read the other case studies n the MS-Selfie site about patients like you? Simply enter 'smouldering' into the search function.
https://gavingiovannoni.substack.com/p/case-study-managing-smouldering-ms
https://gavingiovannoni.substack.com/p/do-you-have-smouldering-ms
Unfortunately, due to your EDSS score you would not be eligible for HSCT. The following Newsletter may be of interest to you:
https://gavingiovannoni.substack.com/p/ahsct-who-should-have-access
Again please use the search term 'AHSCT' in the search bar for more information.
It’s Mary-Ann following up on my post yesterday.
Thank you for sharing this post in relation to my questions about SPMS and AHSCT.
A number of questions arise:
1a) how do I find out about participating in the MS society drug trial mentioned in your post? When are results expected?
1b) Are there any level three drugs you would suggest I consider using and move off Fiilgolimod?
2) I understand AHSCT is not an option on the NHS. However, is it medically possible as a private procedure? (I have a child undergoing treatment for childhood leukaemia -ALL. I have lived with the infection risk and low or negative neutrophil counts for over a year. It would not be a big consideration should I have the AHSCT treatments.
3). My EDSS score is based on an online self completed questionnaire.
It seems that 6.5 is the upper level of a score permitting AHSCT. Why else would you consider my estimated score as a factor excluding me from the AHSCT option?
I posted my questions/circumstances yesterday and your response was most interesting. I hope you’re able to reference the post and your reply.
Thanks for the work you do with MS Selfie. It’s a wonderful source for people like me with MS and my family.
Mary-Ann
1a) how do I find out about participating in the MS society drug trial mentioned in your post? When are results expected?
The trial has not started yet and is due to start later this year. You can watch their website. I will also notify you via this site.
1b) Are there any level three drugs you would suggest I consider using and move off Fingolimod?
In patients with SPMS we may consider siponimod based on it having CNS effects. In subjects not labelled as having SPMS we would do a lumbar puncture and check CSF NFL levels and if raised we would consider subcutaneous cladribine.
2) I understand AHSCT is not an option on the NHS. However, is it medically possible as a private procedure? (I have a child undergoing treatment for childhood leukaemia -ALL. I have lived with the infection risk and low or negative neutrophil counts for over a year. It would not be a big consideration should I have the AHSCT treatments.
Yes, there are private units that would do it almost all-comers, but the risks go up the older you are and the more disabled you are. This is why the London AHSCT set disability cutoffs.
3). My EDSS score is based on an online self completed questionnaire.
EDSS 6.0 is one stick and you have to walk 100 m non-stop. EDSS 6.5 is two sticks to walk 10 m non-stop.
Based on your explanation, I think my EDSS is definitely a six. It may even be a 5.5 as I can walk 10m unassisted non stop. It’s the right and tremors that are a real nuisance.
With smoldering MS would the use of DMT’s slow the progression of the disease. As reference to the following -
‘Whereas smouldering MS refers to both PIRA and other markers of ongoing end-organ damage, such as progressive brain volume loss, grey matter loss, thalamic atrophy, slowly expanding lesions, raised CSF neurofilament levels, cognitive decline, retinal nerve fibre layer thinning, worsening neurological function using neurological stress tests (walking distance, running speed, hand-eye coordination, balance tests, hand-eye coordination, .... ) and other emerging clinical outcome measures and imaging biomarkers. It is important to realise that you can have a stable EDSS (no PIRA) and you can still be getting worse from smouldering MS. This is why I prefer the term smouldering MS to PIRA and don’t refer to them as synonyms. Smouldering MS is so much more than PIRA’.
Relating to progressive brain volume loss, cognitive decline, grey matter loss et. al the other areas you mentioned? Would DMT’s slow these ares of progression of the disease?
Yes, in that DMTs we think anti-inflammatory DMTs stop new lesion formation and hence reduce the rate smouldering pathology accumulates. However, DMTs don't really affect preexisting smouldering lesions and hence don't stop the worsening that inevitably happens.
I suggest you read the following Newsletter that explains these processes:
https://gavingiovannoni.substack.com/p/getting-worse
Thank you so very much for your reply.
Kind regards
Dr. G: Given the fact that HERV transactivates EBV, have you noticed any incidental improvement in fatigue in any people with MS taking the new Pfizer drug?
Other way around EBV transactivates HERVs, i.e. wakes them up from within the human genome.
The COVID-19 antivirals are given for too short a period of time.
When I was Dx'd, they did a spinal tap and drew some CSF.. At the time the doctor told me it was negative for any proteins or filaments.. I had over 100 lesions at that time in my brain but nothing in my cord yet. I am wondering why the spinal fluid would be clear?
Prof G, may I ask what information is derived from NFH results? I read that they are supposed to signify axon loss, not myelin. I have lambda, not kappa paraproteins.
NB. I had to listen three times as your voice is so beautifully soporific that I dozed off...You should record meditation cd's.
Eve