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    Originally posted by REG53 View Post
    This is EXCITING!!
    It really is. In plain language…

    A little background on the dosing of temelimab.

    The Phase 2b trial (NCT02782858) was dosed at 6, 12, and 15 mg per kilogram of weight. The highest dose showed efficacy. Next, a Phase 1 safety trial was organized using a dose of 35, 60, 85, or 110mg per kg of weight in 24 healthy volunteers to see if the higher doses were safe. Happily, there were no adverse events at the higher doses.

    Next, there will be human trials to establish what dose is most effective to halt MS and allow remyelination to occur as a natural process.
    If newly diagnosed with MS, I believe I would check the internet daily to make sure I did not miss an opportunity for the next temelimab trial.

    Of course, this treatment is very, very early in development, however, in my opinion, temelimab may prove to be the closest thing to a cure for MS depending on the definition of cure. My definition of a cure for MS is the halting of progression and remyelination of damaged nerves.

    Only living nerves can remyelinate; dead ones cannot. Once dead, nerves are dead forever. Nerves die over time from becoming demyelinated. However, damaged nerves can and do repair myelin if the mechanism blocking remyelination is suppressed and that is what temelimab demonstrated in small studies… it suppressed mechanisms blocking remyelination which allowed natural processes to form myelin around nerves.

    Yes, it is very early in development but temelimab is looking really good, IMO.

    https://www.neurologylive.com/clinic...erosis-phase-1

    Comment


      Thanks for sharing myoak

      Comment


        Thanks, Myoak. I subscribed to the site. I SO hope the drug is successful so patients like Selma Blair have a better future.

        Comment


          Yes, thank you Myoak.

          In the link you shared, I found this interesting:

          "The clinical trials of the therapy are suggestive of a newer hypothesis about the root cause of MS, which represents early viral DNA incorporated into the human genome millions of years ago. Roughly 8% of the human genome today consists of these viral DNA incorporations.

          “Efficacy of GNbAC1 in MS suggests that the initial viral trigger for MS is not simply an early childhood viral exposure that triggers MS in a genetically susceptible individual. These results suggest instead that the initial viral basis of MS is some of the ancient viral DNA in our genome lying dormant within us that is derepressed by environmental viruses (eg, Epstein-Barr virus),” Daniel Kantor, MD, wrote in a 2018 publication.2"

          But what about the people who didn't contact the Epstein-Barr virus? It uses this as an example (eg) and wonder what other environmental viruses are to blame?
          1st sx '89 Dx '99 w/RRMS - SP since 2010
          Administrator Message Boards/Moderator

          Comment


            Originally posted by Seasha View Post
            Yes, thank you Myoak.

            But what about the people who didn't contact the Epstein-Barr virus? It uses this as an example (eg) and wonder what other environmental viruses are to blame?
            Hello Seasha and All!

            "But what about the people who didn't contact the Epstein-Barr virus? It uses this as an example (eg) and wonder what other environmental viruses are to blame?"

            Although there are a few other infectious causes, both viral and bacterial, which have been speculated to play a role in causing MS, none have anywhere near the scientific support as EBV.

            The MS researchers at BARTS in London flatly state that only EBV infected people get MS. These researchers claim those who have MS and believe they were never infected by EBV were simply not tested thoroughly enough. There are several different ways of checking for EBV antibodies (which give evidence of past infection) and some of those methods of testing for EBV are not 100% reliable.
            As far as what other environmental viruses are to blame, probably none.

            Remember, HERV are not environmental viruses, they are viruses in our genome. The hypothesis behind temelimab is to stop these HERV from replicating. The researchers believe replicating HERV is where the cascade of events resulting in MS begins.

            EBV is proven to be a catalyst for EBV replication. Why is unknown, but it is known that HERV replicate with the help of EBV. So, if there were not EBV, the belief is that HERV would not replicate.

            Why then does not everyone with EBV, which is about 98% of the population get MS? Great question that lies at the root of explaining MS, I believe.

            The most reasonable explanation is because of improper immune response to EBV. One hint that this explanation is on the right tract are studies which show people who had a bad case of mononucleosis (EBV infection) are more likely to get MS than those who don’t.

            If we asked at this site, many people would chime in saying they had a really bad case of mono when they were younger. Of course, they are other examples, this is only one of a less than optimum response to EBV early and seeing MS later in life.

            Why are some immune responses to EBV less robust than others? Partly because of individual genetic differences and partly because of environmental factors. For example, we know low vitamin D is a risk factor for getting MS. Also, we know smoking is a risk factor for getting MS.

            Just a side note on smoking and MS… Swedish smokers who quit delayed SPMS by 8 years compared to those who continued smoking. That is data mined from Sweden’s national registry.

            But back to the main topic…
            So, in addition to blocking HERV replication, temelimab suppressed mechanisms blocking remyelination which allowed natural processes to form myelin around nerves. WOW!

            It will take a few years but this may play out really well. Too early to tell w/o trial data but when data comes, I expect this medicine will have a much, much better safety profile than current MS meds. We just have to wait for the trials and the results.

            I hope this was helpful in explaining a few points. There are finer points made by earlier posts within this thread. This was brief but that’s okay.
            Not to lose anyone but some will find this point interesting, I believe. Different strains of HERV are active (replicating) in different diseases. The HERV seen in MS is simply called MSRV (MS Retro Virus). In other diseases other HERV have been identified.

            So, EBV promoting HERV replication could be a problem in other diseases besides MS. And very likely is, IMO.

            Regarding MS, you can google an in-depth study if you wish… Activation of MSRV-Type Endogenous Retroviruses during Infectious Mononucleosis and Epstein-Barr Virus Latency: The Missing Link with Multiple Sclerosis?

            Comment


              Thanks for the explanation, Myoak!
              1st sx '89 Dx '99 w/RRMS - SP since 2010
              Administrator Message Boards/Moderator

              Comment


                Originally posted by Seasha View Post
                Thanks for the explanation, Myoak!
                You are very welcome.

                I wanted to stress one point...

                But EBV infection does not have to be active to promote HERV replication. Even in a latent state EBV has that affect. Some people never notice symptoms from an infection of EBV. Others have had no symptoms for many, many years from it.

                EBV even in a dormant state promotes HERV replication; studies conclusively prove that point. Many researchers believe the replication of certain HERVs begin a cascade of events which results in MS.

                There is great interest and ongoing activity in developing treatments for that, such as temelimab.

                Comment


                  More temelimab results announced March 12, 2019:

                  GeNeuro announces positive results from two-year study of MS drug

                  https://www.pharmaceutical-technolog...wo-year-study/

                  "Swiss biopharma company GeNeuro has announced that its two-year Phase IIb study of temelimab in multiple sclerosis (MS) confirmed the results from a previous 48-week CHANGE-MS trial where the drug had a neuroprotective effect.

                  The two-year ANGEL-MS study showed that that the drug had a positive impact on MRI measures of disease progression, which included reductions in brain atrophy and maintenance in myelin integrity measured by magnetization transfer ration (MTR) imaging.

                  Patients who completed the CHANGE-MS trial were offered continued treatment in the ANGEL-MS trial once they had completed 12 months of treatment.

                  For the strongest dose group in the ANGEL-MS tiral, 18mg/kg of temelimab, there was a 42% reduction in brain atrophy in the cortex compared to placebo; this rose slightly to 43% in the thalamus.

                  Participants taking the same dose of temelimab experienced consistent improvement in MTR signal across cerebral cortical bands and normal appearing white matter bands.

                  Additionally, the 18mg/kg group showed a lower probability of disability progression measured by the Expanded Disability Status Scale. Only 3.8% of these patients had a 12-week confirmed worsening in neurological disability from baseline in CHANGE-MS trial, compared to 4.8% for the 12mg/kg group, 8.3% for the 6mg/kg group and 9.1% for the placebo arm.

                  GeNeuro CEO Jesús Martin-Garcia said: “We are extremely pleased with this data, which clearly confirm the robust and consistent effects of temelimab on key MRI markers of neuroprotection, and we are excited by the early signs of clinical benefit.

                  “The results of ANGEL-MS confirm the potential of temelimab to act against disease progression, the largest unmet medical need in this indication. It further reinforces our determination to continue the development of temelimab in MS.”

                  Temelimab is a humanised, monoclonal antibody designed to mitigate the effect of a certain human endogenous retrovirus (HERV) called pHERV-W, which is found in the brains of MS patients. Neutralising the virus allows the drug to block the neurodegenerative process and restore myelin integrity in MS patients.

                  The drug was well-tolerated by the trial participants and there were no dose-limited safety signals."

                  Comment


                    This thread has me wondering about temelimab ! Is this drug infused, injected, inhaled oral or what?
                    I have not read all 127 responses but this drug seems to be very promising ! Where do I sign up?

                    Comment


                      Originally posted by JerryD View Post
                      This thread has me wondering about temelimab ! Is this drug infused, injected, inhaled oral or what?
                      I have not read all 127 responses but this drug seems to be very promising ! Where do I sign up?
                      Temelimab used to be called GNbAC1. The drug's name ends in mab, which means it is a monoclonol anti body (mab). All the other mabs used in MS... natalizumab, rituximab, ocrelizumab are administered as infusions; there is no reason to believe temelimab is any different.

                      A Phase 3 trial of temelimab has not yet been organized.

                      Some researchers question how effective this treatment will prove in a large patient population because of the limited amount of temelimab which passes through the blood brain barrier. Only a large Phase 3 trial will tell.

                      The significance of temelimab at this moment for me is... that it is treating HERV and having good results, indicating that viruses may indeed be driving MS, which is the thought behind the Charcot Project, the title of this thread.

                      Michael Pender is taking it one step further and treating why the HERV are activated in the first place... and that is because an improper immune response to EBV allows HERV to replicate in the first place.

                      I'm going to review Pender's work again and explain it in a little more detail in my next post here. And then furnish a link to a recruiting trial which incorporates most of Pender's technique for treating the cause of MS, according to Pender.

                      Comment


                        Please allow yourself a few extra minutes to let this post explain what the cause is for MS and what the cure is, won't you?

                        Yes, this is according to one man's ideas but as time passes more and more scientific evidence is presented confirming his hypothesis that MS is caused by an inadequate immune response to EBV. And, by improving immune response to the level of those who have EBV and DON'T get MS, you can cure MS. Here is my explanation in layman's terms...

                        Dr. Michael Pender firmly believes a person has MS because their body does not have enough killer T cells (CD8) to control EBV (Epstein Barr Virus) infection. He is convinced that most of the 90% plus of the world who have been infected by EBV does not have MS because their bodies have enough killer T cells (CD8) to control the Epstein-Barr Virus.

                        Pender formed his hypothesis in 2003 that Epstein Barr Virus is the cause of Multiple Sclerosis and has made made several notable predictions based on his hypothesis which have proven true.

                        (1.) Pender correctly predicted that EBV infected B-lymphocytes would be found in the brains of people with MS.

                        (2.) Pender correctly predicted that treatments such as rituximab which deplete B-cells would be effective in MS.

                        (3.) Pender correctly predicted that people with MS would have a decreased CD8 killer T cells controlling EBV; a fact which has been proven over the last 12 years.

                        (4.) Pender predicted that not only rituximab would be effective treating MS but treatment specifically targeting EBV would be effective treating MS. This is called “adoptive immunotherapy” and describes what Pender is currently doing by withdrawing circulating blood, treating it to increase killer CD8 T cells which are capable of controlling EBV, and infusing treated blood back into the patient to kill EBV and switch off the autoimmune attack we call MS. Pender calls this “EBV specific T cell therapy”.

                        In the link provided here Pender describes the first MS patient in the world he treated with EBV specific T cell therapy. Pender goes on to talk about his ongoing study involving additional patients.

                        https://soundcloud.com/bioanalysis-z...osis-treatment

                        Thus far, a pwMS’s clinical response in Pender’s trial is based on one thing… EBV reactivity to the T cells infused back into the patient. A total of 20 million killer T cells were infused in each patient at a rate of 5 million per week. However, EBV reactivity to those T cells ranged from 1% to 48% in various patients. Those whose EBV reactivity was 1% showed no improvement. Those with higher reactivity showed great improvement.

                        Clinical improvement in MS increased according to EBV reactivity. The greatest improvement was seen in a patient with 48% reactivity who went from walking 100 yards to walking 1 mile. More info on the first patient Pender treated and 6 subsequent patients is presented earlier in this Charcot Project thread.

                        Please understand Pender believes EBV specific T cell therapy based on EBV reactivity can cure MS.

                        If the EBV in the body of a person with MS reacts to killer T cells and there are enough killer T cells to control EBV infected B lymphocytes, that person will no longer have MS, that is Pender’s position. In the next post in this thread I will present a link to an ongoing trial involving this method which is still recruiting for anyone interested.

                        If there is one post in this entire thread to spend a few extra minutes contemplating, I hope you do so with this one. Pretty cool if Pender has the answer for MS. I believe he does.

                        Comment


                          Thanks Myoak! You are teaching algebra to a monkey !
                          There's something that I am trying to get straight, though. The EBV has been around forever. I think that I was taught that the EBV was largely harmless. Yet, Dr. Pender has focused his efforts on EBV and its role in causing MS.
                          What's next ? The gall bladder in some humans causes MS?

                          Comment


                            Please let me explain something about this new trial...

                            In Pender's trials, Pender used a patient's own blood, treated it to enhance Killer T cells and infused that blood back into the same patient.

                            In this trial being done by Atara Biotherapeutics they are trying something slightly different from Pender. It is my understanding that Atara took blood from healthy donors, treated it to enhance killer T cells, and that product which is called ATA 188, will be infused into the trial participants. The hope is that using this product "off the shelf" will greatly reduce both time and money over Pender's technique of treating a patient's own blood. Of course, some may argue that using a patient's own blood is one of the keys but that is entirely unknown until this trial's results are in.

                            Also, please note that even using a patient's own blood, response in Pender's previous small trials depended entirely on how reactive a patient's B lymphocytes were to the re-infused T cells. Pender is working on ways to enhance response in those whose B cells were not affected. Keep in mind that those who did have good B cell reactivity to the re-infused T cells responded dramatically well.

                            The trial is recruiting only 60 patients total at 7 locations. 3 places in Australia (Pender is leading one of those) and 4 locations in the US, Philadelphia, Baton Rouge, Houston, and Scottsdale AZ.

                            The inclusion and exclusion criteria along with exact trial locations are in the link.


                            https://clinicaltrials.gov/ct2/show/...83826#contacts

                            ATA188 is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ progressive and relapsing forms of MS.

                            Adult subjects with either progressive forms of MS (Population A) or with Relapsing Remitting Multiple Sclerosis (Population B) will be enrolled. Subjects will be treated with ATA 188 via IV infusion.

                            Please read both the inclusion and exclusion criteria thoroughly.

                            Notably, they are taking some people up to age 65, if criteria are met.

                            Perhaps, one person not presently on a DMT will read this post, contact a trial location, and ultimately change their life forever. If that is you and you do not come back to this thread and let us know, I will haunt you!

                            For the rest of us, what we learn from this trial may shape MS treatments, hereafter. And, may lead to tossing the present DMTs.

                            Comment


                              If I may be a bit reflective here…

                              I realize much of this is difficult to understand and most of it is boring, also.

                              But seldom have I become so convinced about an issue. I truly believe Pender’s hypothesis is correct that an improper immune response to EBV begins the cascade of events which ends in MS and his enhanced T cell solution to defeat the problematic B cells infected by EBV is the solution to MS.

                              Decades of study as a non-professional has led me to believe that Pender is right. Tears of compassion for those who suffer from MS and feeling helpless to alleviate their suffering drove me into late hours many nights investing more time than most doctors could afford searching for anything that might benefit someone with MS. I became more and more engrossed attempting to understand a disease with a mind-numbing number of nuances.

                              What I found along the way were many, many others doing the same and largely for a similar reason… an incredibly strong belief that no one should suffer from MS. I felt instilled with the steadfast belief in ‘seek and ye shall find’ as a principle immutable as the law of gravity and a rock-solid belief solutions are wanting to be found. Everything I know I learned from others.

                              MS can be solved. All the pieces can be put together. As more people become convinced that Pender has a big chunk of the MS puzzle, assistance will gravitate in his direction, as we see in this trial by Atara Biotherapeutics.

                              We will see the cure for MS, I believe, and it won't be 10 years from now, either. Pender gives us a glimpse today.

                              Comment


                                Myoak, thank you for posting this. Excellent information for us all.

                                Originally posted by Myoak View Post
                                The Charcot Project will investigate the possibility that MS is caused by a virus. Simple, yet the implications are profound. Because if true treatments for MS would be radically altered.

                                For years it was thought that stomach ulcers were caused by stress, foods, etc. The idea that stomach ulcers might be caused by bacteria was laughable to some, and pretty much disregarded by everyone else. Then someone purposefully infected himself with bacteria, got an ulcer, treated himself with antibiotics, got rid of the ulcer and shocked the medical community. Conventional approaches to disease treatment can get relegated to the trash heap overnight when significant discoveries are made.

                                Those who want to know more about the Charcot Project may do so by viewing an introduction of it on YouTube at http://www.youtube.com/watch?v=GTD1Bp-LZk44


                                IMHO, it is unlikely any of the major drug companies currently making money from expensive MS treatments will spend any effort looking for what Charcot Project seeks… a viral cause for MS and an effective viral treatment for it. I wish them Godspeed.

                                I found the YouTube video outstanding. Kind Regards.

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