Barts-MS rose-tinted-odometer: ★★★★★
I have been asked many times if we can cure someone who has MS. I have tried to explain what an MS cure may look like many times on this blog and have actually published articles defending the definition.
I explained in a previous post that you may be cured of your MS, but still, have worsening or progressive disease. The difference between progressive disease, which is due to previous MS damage and ageing is that the former should burn out, i.e. after a period of time, your worsening disability should eventually stop or flat-line. In comparison, MS-induced premature ageing is unlikely to stop. In comparison defining a cure in people who are young, with reserve capacity, who have been treated earlier is a much easier task.
From a biological perspective you can be cured but still have neurological deficits from previous damage, which need to be targeted with so-called ‘repair’ and ‘neuroregenerative’ therapies. These are separate processes and are independent of a so-called biological cure.
Based on our current understanding of MS a cure can only really occur in relation to IRTs (immune reconstitution therapies; e.g. alemtuzumab, cladribine & HSCT), i.e. treatments that are given as short courses that address the underlying ‘cause’ of MS. Maintenance treatments that need to be given continuously can’t cure MS, because when you stop the treatment MS disease activity tends to return and in some cases, particularly with anti-trafficking agents (natalizumab and fingolimod), to a greater extent than before, which we call MS rebound.
For arguments sake let’s say we have treated a group of pwMS early in the course of their disease with an IRT and they have gone into long-term remission with no evident disease activity (NEDA). How long should we wait before declaring a victory over their MS; 10, 15, 20 or 25 years? In the past, we have proposed defining a cure as NEDA at 15 years post-treatment as a starting point (see our MSARD Editorial below). Why 15 years? This is the most commonly accepted time-point used for defining benign MS and therefore it is a standard end-point that could potentially be accepted by the wider MS community. However, this may be wishful thinking many in the field are saying that we can’t cure MS, therefore, we should not even be having this discussion. Do you agree?
The average time to the onset of secondary progressive MS is ~14-15 years so one would expect to see a significant proportion of people manifesting with SPMS in this 15-year timeframe. If we have gotten the autoimmune hypothesis wrong and IRTs don’t work then I would estimate at least a third of treated subjects should have SPMS at 15 years. The problem with 15 years is that it is a long wait if you have MS. Many pwMS want to know ‘now’ if an IRT offers a cure, therefore we need data to convince the naysayers to support the ‘cure hypothesis’. Hopefully, convincing data, such as the HSCT data below, will change their minds and get them to at least offer IRTs to more of their patients.
In the past, I have proposed a deep phenotyping project to look at pwMS who are NEDA-2 post-IRT to see if we can find any evidence of ongoing inflammatory, or neurodegenerative, MS disease activity. I proposed interrogating them in detail and comparing them to a similar cohort of pwMS who are being treated with maintenance DMTs. Deep phenotyping is simply a term that refers to the interrogation of the CNS to see if the IRT has stopped ongoing damage and protected reserve capacity.
The study that has come closest to reaching this 15-year time point is the Canadian myeloablative HSCT cohort (see below). Mark Freedman, the principal investigator, has told me that all of these patients remain NEDA-2 (no relapses or MRI activity) although some have worsened in relation to their disability, which may be a result of previous damage and not ongoing MS disease activity. However, the most impressive observation is that this cohort of patients, who all had very active MS prior to HSCT, has ‘normalised’ their rate of brain volume loss or atrophy after an initial precipitous drop in brain volume due to pseudoatrophy and/or chemotherapy-induced neurotoxicity. Mark Freedman has also said that about a third of these patients, who have had lumbar punctures, have lost their OCBs (personal communication). However, the spinal fluid analyses have all been done quite early after HSCT hence we don’t know how many subjects who have reached 10 years of follow-up or more have persistent OCBs. Wouldn’t this be an interesting fact to know?
When the 10-year lumbar puncture and spinal fluid analysis was done in a group of Polish subjects treated with intravenous cladribine, 50% had lost their spinal fluid oligoclonal IgG bands (OCBs) at 10 years and this group of OCB-negative patients tended to have stable disease compared to those who hadn’t lost their OCBs. This is why we are doing the SIZOMUS (Ixazomib) and the DODO (high-dose ocrelizumab) studies to try and scrub the CNS clean of pathogenic B-cells and plasma cells that may be driving low-grade smouldering MS. Exciting? You bet! These two studies are one of the reasons I get up in the morning, look at myself in the mirror and say nobody can say Barts-MS isn’t doing innovative MS research.
The question I am now asking myself is switching a definition of a cure to a biological one a better strategy? This is a new line of thinking that has been brewing in my head for the last 12 months or so. If EBV is the cause of MS can we simply put pwMS into remission and clear them of EBV? This is why I want to do the iTeri and similar studies, i.e. to give an IRT and follow it with a drug that prevents EBV reactivation (antiviral) or scrubs B-cells of EBV (EBNA-1 antagonists).
I am sure many cynics will be saying no not Prof G thinking aloud. Yes, I am thinking aloud. If only a minority of pwMS treated with IRTs go into long-term remission why can we increase the proportion by using the induction-maintenance approach that targets the cause of MS? What do you think?
If you agree with this strategy I am going to need help to get the iTeri concept study funded.
DEFINING A CURE:
Banwell et al. Editors’ welcome and a working definition for a multiple sclerosis cure. Multiple Sclerosis and Related Disorders. 2013; 2(2):65-67.
…. Defining a cure in MS is a difficult task. How long should we wait before declaring a victory; 15, 20 or 25 years? Oncologists have back-tracked on this issue and instead of a cure they now prefer to use the term NEDD, or no evidence of detectable disease, at a specific time-point knowing full well that a limited number of subjects will relapse and present with recurrent disease after this point. We propose using the term NEDA, or no evident disease-activity, at 15 years as a starting point for defining a cure. Why 15 years? This is the most commonly accepted time-point used for defining benign MS and therefore it is a usual endpoint. In addition, the median time to the onset of secondary progressive MS is ~10-11 years (Kremenchutzky, Rice et al. 2006) and is well within the 15-year time window of our proposed definition of a cure. At present NEDA is defined using a composite of a) no relapses, or b) no EDSS progression, or c) no MRI activity (new or enlarging T2 lesions or no Gd-enhancing lesions) (Havrdova, Galetta et al. 2009; Giovannoni, Cook et al. 2011). This description is currently based on data that is routinely collected in contemporary clinical trials (Havrdova, Galetta et al. 2009; Giovannoni, Cook et al. 2011). The definition of NEDA will evolve with technological innovations and clinical practice, and in the future, it will almost certainly include MSer-related outcomes, grey matter disease activity, an index of brain atrophy and hopefully a CSF biomarker profile…..
References:
Giovannoni, G., S. Cook, et al. (2011). “Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis.” Lancet Neurol 10(4): 329-337.
Havrdova, E., S. Galetta, et al. (2009). “Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study.” Lancet Neurol 8(3): 254-260
Kremenchutzky, M., G. P. Rice, et al. (2006). “The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease.” Brain 129(Pt 3): 584-594.
THE CURE #1?
Atkins et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016 Aug 6;388(10044):576-85.
BACKGROUND: Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis.
METHODS: We did this phase 2 single-arm trial at three hospitals in Canada. We enrolled patients with multiple sclerosis, aged 18-50 years with poor prognosis, ongoing disease activity, and an Expanded Disability Status Scale of 3.0-6.0. Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim. Immunoablation with busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin was followed by aHSCT. The primary outcome was multiple sclerosis activity-free survival (events were clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, and sustained progression of Expanded Disability Status Scale score). This study was registered at ClinicalTrials.gov, NCT01099930.
FINDINGS: Between diagnosis and aHSCT, 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans. Median follow-up was 6.7 years (range 3.9-12.7). The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6% (95% CI 46.6-84.2). With up to 13 years of follow-up after aHSCT, no relapses occurred and no GdGd-enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans. The rate of brain atrophy decreased to that expected for healthy controls. One of 24 patients died of transplantation-related complications. 35% of patients had a sustained improvement in their Expanded Disability Status Scale score.
INTERPRETATION: We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs. Furthermore, many of the patients had substantial recovery of neurological function despite their disease’s aggressive nature.
THE CURE #2?
Rejdak et al. Cladribine induces long lasting oligoclonal bands disappearance in relapsing multiple sclerosis patients: 10-year observational study. Mult Scler Relat Disord. 2019 Jan;27:117-120.
Background: There has been long-term interest in cladribine as a drug for the treatment of MS. The current study focused on the effect of cladribine on oligoclonal bands (OCB) expression in the CSF in relapsing-remitting MS (RRMS) patients observed over 10 years.
Methods: 29 treatment-naive subjects with RRMS were prospectively enrolled and received induction therapy with subcutaneous parenteral cladribine (at a cumulative dose of 1.8 mg/kg; divided into 6 courses every 5 weeks given for 4-6 days, depending on patients’ body weight). Selected patients received maintenance doses in the follow-up period.
Results: Isoelectric focusing revealed that 55% of patients did not have OCB in CSF after cladribine treatment as compared to baseline testing when 100% of patients were positive for OCB. There were no significant differences in Expanded Disability Status Scale scores at baseline and at the end of treatment cycle between OCB-positive vs. OCB-negative subgroups. At the last follow-up, OCB-negative patients had lower disability compared to OCB-positive patients (p = 0.03).
Conclusion: Cladribine-induced immune reconstitution leads to long lasting suppression of intrathecal humoral response, which might be an additional mechanism that enhances the therapeutic effect on disease progression in RRMS patients.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
Fascinating. Sadly I’m all too aware that delaying treatment on an effective DMT leads to permanent damage/disability. I haven’t had an attack since starting Tysabri 12 years ago but 14 years of constant relapses before then has caused permanent disability. I don’t think there will be any treatment that can restore my limited walking or bladder/ bowel damage during what time I have left. However, it’s fantastic that younger patients can now get treated shortly after dx and lead a normal life without disability.
I am quite late to the party, but I just wanted to tell you that I am deeply touched by your compassionate attitude towards future generations, even throughout times of hardship. I wish you all the best.
Thank you for still posting.
“The problem with 15 years is it is a long time to wait if you have MS. Many pwMS want to know ‘now’ if an IRT offers a cure..”
PwMS are obviously desperate to avoid disease progression but, realistically, the path to a cure in modern diseases rarely involves a Hollywood style magic bullet (Cancer is a good analogy). Science stumbles forward, but that “stumbling” is rooted in good science, research and data harvesting. Progress is just going to be piecemeal, rather as it is in the fight to overcome SARS-Cov-2. PwMS need patience but it must be hard when one knows one is deteriorating.
If you have been thinking this particular matter over for a year, Prof G, you must be fairly sure that it is worth pursuing in research terms. But who will fund this research? Is there any likelihood that organisations like the MS Society will divert some of the huge sum they have committed to spend on MS, or has it all been earmarked? What funding streams are open to BartsMS Research?
MS funding has been hit in 2020 and will be more limited in 2021…we missed out on the ~£4,000,000 destined to go Cambridge and Edinburgh awarded in Feb 2021, but the call was not for clinical stuff that we do:-(
What’s the difference between a ‘cure’, ie NEDA on MRI but possible progression of symptoms due to aging, and SPMS ie NEDA in MRI with progression (possibly very slow).
I am 20 years from probable first MS symptoms and NEDA a year post second round of Lemtrada. I feel reluctant to treat this as a cure as I know I could just as easily be in SPMS.
Read this over a glass of wine….my daughter made me feel guilty about being on my phone during moana but it was worth it. Feeling optimistic. A question though Prof….knowing what you know about upcoming trials and drugs in development – would you still go for HSCT or Alemtuzumab as your particular poison over for instance…..Ocrevus (to target relapses) and the Sizomos trial (to hit the smouldering element)? Also….is the myloblative protocol used in HSCT now. I was under the impression that most centres were non-mylo?
“Also….is the myloblative protocol used in HSCT now. I was under the impression that most centres were non-mylo?”
Think in Sweden they’ve used both but most hsct center India..Mexico..Israel..Russia..Bulgaria… all use non-mylo because using more chemo just causes more brain toxicity and doesn’t improve results. just look at Dr. Freeman’s study above…70% failure rate just like non-mylo. And he criticised Dr. Burt’s protocol as being “Chemo Lite” ….”The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6%”….”We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis.”..
Why does hsct fail in 30%…because hsct only targets b and t cells in CNS…hsct doesn’t target EBV…so if a person doesn’t have enough cd8 tcells to control EBV..it EBV and MS simply resumes post hsct.
“This is why we are doing the SIZOMUS (Ixazomib) and the DODO (high-dose ocrelizumab) studies to try and scrub the CNS clean of pathogenic B-cells and plasma cells that may be driving low-grade smouldering MS. Exciting? You bet! “
Good to see Prof G back to his best. Please leave Prevention in the capable hands of Dr Ruth. You’ve still got work to complete on “curing” MS.
Are there similar issues (defining a cure) with diseases such as arthritis and lupus (where ebv may also be involved)? Is IRT / maintenance therapy used for these diseases?
What’s happening in the MS repair research area given so many disappointing results over the last 18 months?
MS Soc have funded Cambridge and Edinburgh £4,000,000 and have funded clemastine & metformin trial
Seeing how the PwMS crowd goes wild anytime EBV is mentioned, how come there aren’t any EBV/HAART funded by MS Soc or any other MS orgs?
Because neurologists are not virologists…and know little to nothing about EBV..and would have no idea how to design a therapy that worked against EBV.
At what time point after treatment does it make sense to look and see If the OCBs are gone following IRT?
We (ProfK) are doing this
Could i ger som more color here? Is this a study? When do tpu think this is work is complete? Reason om asking is that im 2 years post Mavenclad soon and was thinking about asking for a lumbar myself
The cure 3
Can multiple sclerosis be cured? A case of highly active relapsing multiple sclerosis
treated with autologous hematopoietic stem-cell transplantation 13 years ago.
Abstract: A 26-year-old man, with five years of highly active deteriorating relapsing
multiple sclerosis (MS), unresponsive to conventional therapy, was treated with autologous
hematopoietic stem-cell transplantation (AHSCT) 13 years ago. Since then the patient had
no clinical or neuroradiological disease activity and disability progression was halted.
Repeated analysis of CSF revealed reduced levels of inflammatory biomarkers and the
neurofilament light protein level was normalized indicating no further axonal degeneration.
The patient is socio-economic independent, is working full time, and has become a father.
Measures of quality of life and cognition did not indicate further deterioration. Long-term
follow-up has not shown any signs of active disease suggesting that AHSCT may be a cure
for MS.
https://pubmed.ncbi.nlm.nih.gov/32570177/
Cure 4
Well world, can not believe it myself, but tomorrow is my 20th anniversary from having my HSCT, Hematopoietic Stem Cell Transplant for MS, (Multiple Sclerosis). And my first reason I believe politics and science do not make good bed fellows.
If you don’t know my story, I was diagnosed with MS in 1995. I went from being a totally healthy young woman to a very sick woman quickly, with two spirited young sons, who were at the time, 6 and 8 years old, I had to do something different than the medication that wasn’t working. I quickly went from remitting relapsing, to secondary progressive. My symptoms of: drop foot (left side), voice tremors, body tremors, hot and cold sensitivity, no bladder control, no equilibrium, no energy, double vision, sleep issues and deep depression, were getting worse by the day.
On March 31, 2000, I had my Stem Cell Transplant using my own stem cells. I was a total experiment based on medical results of past people who had both cancer and MS. When those cancer patients went through bone marrow transplants or stem cell transplants, not only did their cancer go away, but their MS started to abate. It made total sense to me. MS is my immune system attacking itself, so kill the old immune system and build a new one. Like rebooting your computer. I was desperate, and declining fast, so I decided to go ahead, fingers crossed, to be the second person in California, with no cancer, to do a complete Stem Cell Transplant, to see if my MS would go away. Again, fingers crossed. Thank God, the science worked.
At the time our president, Bush Jr. decided that stem cell transplants were, as he put it, “messin with God.” So, on August 9, 2001, he introduced a ban on federal funding for research on newly created human embryonic stem cell lines, which pretty much shut down all Stem Cell research. Thank the same a God, I had already had my transplant, and was already increasingly getting better and, by the way, have continued to get better every year since. So many people that could have been helped, had to wait, until President Obama realized the mistake that Bush made, and reversed it. Which aloud Stem Cell research to begin again in the US.
If you knew me back before my transplant, I was walking with a cane, couldn’t talk, and wanted to just stay in bed. You would be surprised to see me now! I’m performing comedy, playing golf and living a life I never thought would be possible, 20 years ago.
Conclusion… science and politics do not mix. Presidents should not be making decisions on medical issues, EVER! Please leave the major medical decisions to the doctors and people who know what they are talking about, and can act without religious prejudice or fear of looking bad. Religion and Egos should be left completely out of the medical equation.
I’m so grateful to my husband for being here and having the ability to help me get it done
One of the first person to be treated with hsct myeloablative regime and radiation
https://www.facebook.com/sandiselvi/posts/10159610217757166?comment_id=10159612948547166&reply_comment_id=10159612953497166¬if_id=1585667487082947¬if_t=comment_mention
Wow, great approach!
Sign me up for iTeri 😉 4 years remission after aHSCT, now some disease activity and high level of EBV antibodies (igg). Could this mean that EBV wasn’t erased by chemotherapy and get reactivated?
“4 years remission after aHSCT, now some disease activity and high level of EBV antibodies”
Yes…the 4/5 year it seems is where hsct starts to fade..Yes hsct doesn’t get rid of EBV..it just
slows it down for 4/5 years.
“The transplant saved my life–I was, and still am, beyond fortunate. For four years it helped me feel almost normal again. And I purposefully took every advantage, living life with my right foot firmly on the accelerator, figuratively and literally. It allowed me to drive again, travel the world again, and even snowboard again. But I knew that I might have to write this post one day.
As evidenced by the just released 3-year update of HALT-MS in JAMA Neurology, the success rate of the trial has been unprecedented in MS, with nearly 80% of patients showing no evidence of disease activity after three years, and with some patients seeing a marked reversal in disability, myself included (2.5 EDSS points!). Unfortunately, it appears that with time the treatment’s durability is tested, as early numbers suggest fewer than 70% exhibit zero disease activity (relapse, new lesions or EDSS increase) at year four, a figure that drops below 60% at year five. Still powerful results, but far from across-the-board remission.”
https://forums.activemsers.org/forum/activemsers-org-forums/dave-s-sct-journey/1826-gains-from-my-transplant-are-slipping-begrudgingly-weighing-plan-f
S1P1 Modulators seems not to fit in this picture, do they still have any use? And do you still use them in your clinical-practice? Why?
Thank you for this kind of posts I like them and make the future a bit more bright.
About the induction maintenance approach I have two concerns: when and how we define that the induction work? If it doesn’t, then we may be mislead thinking that maintenance is not working. Second, why doing induction maintenance instead of treating again?
Regarding aHSCT I think we should also ask what are the differences between people in long term remission and those who have recurrence of disease activity. Was the treatment unable to kill all the guilty cells or was the immune system of that person very prone to autoimmunity so that he redeveloped MS ex novo?
What I think we really need is an effective biological marker that can say disease is active or gone. Do you think that OCB status could do the job? Have you thought about a collaboration with dr Airas to do a PET scan for SIZOMUS patients and see microglia activation?
Love this Prof G. The iTeri idea is super interesting after i have come to the conclusion that HSCT is my ‘best-shot strategy within 5 years of my diagnosis (informed mostly by this blog’s insight and after seeing my family member suffer for two decades and ultimately pass away from MS complications at the not-so-old age of 65). Im interested in finding out what is the element that makes people fail HSCT and how can we improve the non responder rate, and what is that telling us about the cause of MS.
Your gamblers analogy is also in the back of my mind. I’m currently playing with some pretty average odds of remaining in remission (70% chance of being progression free at 10 years, it’s hard to pass up the chance. Perhaps if we had these iTeri etc add-ons on offer, more pt’s like me would feel more at ease with a Clad/Alem + add on strategy to increase our odds of longer term remission, without flying half way around the world to pay a lifetime’s savings for hsct. Sign me up!
“Im interested in finding out what is the element that makes people fail HSCT and how can we improve the non responder rate, and what is that telling us about the cause of MS.”
People who started hsct w/low levels of cd4 and cd8 tcells..t cells that control EBV..were the ones who relapsed post hsct.
So it tells us EBV causes ms..patients w/low cd4 and cd8 will relapse no matter what
treatment is given..unless it is something that totally removes ebv..and as of now there are no
anti-virals that can do this.
“haematopoietic stem cell transplant resulted in 69·2% of subjects remaining disease‐free without evidence of relapse, loss of neurological function or new magnetic resonance imaging (MRI) lesions to year 5”
“While none of the treatment effects studied correlated with clinical outcome, patients who remained healthy throughout the 5‐year study had significantly higher absolute numbers of memory CD4 and CD8 T cells in the periphery prior to stem cell transplantation.”
https://onlinelibrary.wiley.com/doi/full/10.1111/cei.12985
In other words you need high numbers of cd4 and cd8 t cells in the periphery..in order to stay
in remission…as these are cells that control EBV…it tells you that EBV causes ms and that
hsct does not act on EBV by itself…as you need hsct + cd4/cd8 t cells in order to stay in remission.
google pender ebv cd8 for more..your welcome..
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270541/
Thank you! Appreciate the info
So after thinking on this i have a question.. (and pardon my ignorance) but is the proposed mechanism of action for HSCT (or induction therapy generally) to hopefully regrow the B cells without the MOG antigen memory? While the EBV infected b cells may regrow , but will be mediated by the cd4 cd8 T cells? My very unscientific brain is confused!
“the proposed mechanism of action for HSCT”
The chemo removes b and t cells and all inflammation..so idea is that the cells will repopulate in an
inflammatory less environment and not be auto-reactive…which should get you down to normal level of yearly brain loss as opposed to DMT which does not..except Alemtuz.
“While the EBV infected b cells may regrow , but will be mediated by the cd4 cd8 T cells?”
…Yes this is Pender’s view..currently tested by Atara Bio…they have to use genetically matched donor t cells..as the ones people w/ms have are too exhausted to react to EBV. It is mono therapy and does not involve hsct.
They exclude..”Any previous treatment with alemtuzumab, stem cell transplant, or EBV T-cell therapy for both parts and cladribine for Part 2″
Which tells you those are the most effective and they don’t to see people improving from hsct and clouding the trial results.
https://clinicaltrials.gov/ct2/show/NCT03283826
I am so happy as always to read that you’re trying desperately to find a cure and alleviate the suffering this disease ravages on too many people globally. Thank you for that.
My question is, what antiviral actually works against reactivation of EBV?
“My question is, what antiviral actually works against reactivation of EBV?”
Exactly..don’t think there is one..
And what’s more where is the proof that IRT removes EBV in the first place..?
Maybe test this EBV wonder-drug on it’s own before putting it in a 2 stage trial…
This is how trials go up in flames/waste time and tons of money…
“Mark Freedman, the principal investigator, has told me that all of these patients remain NEDA-2 (no relapses or MRI activity) although some have worsened in relation to their disability, which may be a result of previous damage and not ongoing MS disease activity.”
Something is way off here…yes none had relapses or mri lesions but they progressed..In the
Lancet study it says only 70% were free from progression..so only 16 out of 23 had no progression..results that are right in line with non-myelo hsct..which is far less neuro-toxic.
“With a median follow-up of 6·7 years (range 3·9–12·7), 16 (70%) of 23 patients were free from further progression and many patients had improvements in disability.”
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30169-6/fulltext
“We postulated that the failure to control multiple sclerosis resulted from the inability of a mild conditioning regimen to achieve adequate immunodepletion and that greater immunoablation would lead to better outcomes.”
Have to say the results here prove the opposite that more chemo is not the cure for ms..
What you need is just enough chemo to induce neutropenia..and then something to rid the body of EBV.
What are ms cure tests..? Simple just test EBV antibody levels.