ATA 188 for Multiple Sclerosis (anti-EBV neurogenic t-cell therapy from Atara Biotherapeutics)

[@DrMarwaKaisey]

thanks for the fantastic summary of this novel form of treatment. excited to see where it goes!

[@DrBrandonBeaber]

Thanks :) Annette is planning to start recruiting for this study at LAMC soon.

[@jasonc5289]

Now, you're thanking somebody that ranks, at best, 37th. Look up what I'm saying, doctor, and I use that term loosely. World Health Care organization. Look it up. If you're not a fan of the WHO, there's another study from 2017 where "we" ranked 54th with Macedonia coming in 55th; but that study is from 2017 so I guess that you have to take that into account. Nobody should have to go through this, period. American doctors are insanely weird. So weird.

[@PavelProuzaCZ]

Thank you for sharing, Dr Beaber, this is absolutely amazing to see! Looking forward to seeing this treatment trialed also with relapsing MS. The results look incredibly promising.

[@DrBrandonBeaber]

This is definitely exciting research. Maybe in a few decades, an EBV vaccine could dramatically reduce the prevalence of MS.

[@matm6325]

mRNA is on the way for EBV! Hope it’s 10 years not 20 given how fast biotech is moving these days.

[@ramazan9857]

@@DrBrandonBeaber meaningless after 20 years after so many people died

[@suzanneknepp849]

I am glad to see treatments available for those with SPMS. At this time there seems no hope for treatment for those who have SPMS. Also, as people are living longer the upper age limit for clinical trials should be considered to extend to the age of 70. Just a thought.

[@KaitAC]

After reading the study that came out last Thursday, I had a feeling this was coming today!

[@DrBrandonBeaber]

This was a pure coincidence. I filmed this weeks ago :)

[@KaitAC]

@@DrBrandonBeaber oh wow, great coincidence.

[@abq5525]

You’re an amazing person Dr. Beaber. This is great information, and thank you for your dedication. We’re so lucky to have you.

[@DrBrandonBeaber]

I'm glad you enjoyed it. Let me know if you have any video suggestions.

[@SmileyTheAxolotl]

Thank you for this video! As usual, your explanations with graphs, etc are so helpful. I'm very excited to see where this trial goes!

[@DrBrandonBeaber]

:) I am excited to see the results as well

[@MsCmeehan]

Sounds like it could prove to finally be something useful for progressive MS. Great,y needed. Will wait for outcome.

[@07broly]

I'm so excited for my clinical trial for this!

[@jenniferwallace8556]

This video is shaking me to my core. Gives me so much hope!! Thank you!!

[@DrBrandonBeaber]

:)

[@tonyrogic5411]

Thanks Dr, for someone with PPMS it’s great to see some work being done on this. It sounds like it could be a viable future treatment ✅

[@DrBrandonBeaber]

Indeed. I give a lot of credit to Atara for doing their first trial in progressive MS.

[@barbaradascalos4411]

But it started with one compassionate care case and then a 10 person one million dollar trial all funded by MS Australia. Atara then came onboard. Question is why only a start up drug company was willing to invest and none of the Big Pharma like Merck were..???

[@DrBrandonBeaber]

@@barbaradascalos4411 I have no idea. Why did Moderna beat so many other pharma giants to a covid-19 vaccine? Sometimes small companies make magic.

[@quantumdecoherence1289]

Excellent overview. EBV has been implicated in MS pathogenesis for many years yet we are just now researching its role. It is important to realize that IF EBV is the cause, eliminating it via Moderna's Phase 1 mRNA vaccine trial against EBV will likely not reverse disability. But it's a step in stopping the progression. For reversal of established disability, we need ways to regenerate axons, not just remyelination. We're quite a ways away.

[@matiouz07]

Not so far away, NVG 291 looks promising. Phase 2 should start this year !

[@RobertRomeopctech]

Ive had mono as a kid, got ms now. On kesimpta. This is awesome

[@samhouston1483]

Tevogen Bio is working on this too. Very interesting stuff

[@spencerd9325]

Doc, can I ask why you never release any information or potential for helping MS victims that have disabilities? I imagine there is some research on helping those that have disabilities, no?

[@adrianaluciacespedes9252]

Good explanation. What I worry about is.. if you need a donor, the treatment won't be accesible to everyone.. Also, in the meantime.. are there ongoing studies with extisting antivirals? I know there's no interest in trying existing drugs by the pharmaceutical industry but what about goverments and societies ... it will be an "easy short" trial because the safety problem has already been adressed.

[@OmnipotentEnt]

My understanding is that there are a wide range of donors that the company can use to create products that will be compatible for a wider range of people. Someone with more knowledge, please correct me!

[@DrBrandonBeaber]

@@OmnipotentEnt This is correct.

[@klzeller]

Thanks again for another easy to follow explanation of EBV. I never had mono but my sister did. Now I understand how I could have had EBV but no symptoms. My sister and I both have MS diagnosed decades apart.

[@DrBrandonBeaber]

Most people who have had exposure to EBV had no clear symptoms

[@Skypods1]

at age 19 I had mononucleosis the kissing disease 🦠 ebv positive and that fatigue and weakness is comparable to my fatigue and weakness now. 10 yrs after ebv infection I was diagnosed with multiple sclerosis. I’ve got the progressive type EDSS 6.5 from 1.5 15 yrs ago.

[@SaraC-us5ky]

My MS showed up 7.5 years after mono, 14 days after I’ve had contact with my mom in the hospital, as she was having an herpetic encephalitis. 2+2=4…

[@CherylsStampinSquad]

This is such exciting news! Makes me hopeful!

[@jasonmace8086]

Great video thank you so much for sharing .... I'm confused however, the infected B cells once they are attacked by the donor T cells and numbers reduced is the host at risk for a future EBV infection? Is the improvement above B-Cell depleters related to crossing the blood brain barrier and/or does the T cells attack a greater variety of infected cells than current CD20 therapies?

[@randholtham8493]

This is great I’d try it today if I could!! I’m at least glad to know what the state of the art is! I would not know if not for your channel!

[@DrBrandonBeaber]

:)

[@hackett1181]

Thank you! I am hopeful…

[@patfeller6690]

I was tested with a very highly EBV level and started taking Thymosin Alpha One. It helped dramatically. Could you do a video on Thymosin?

[@DrBrandonBeaber]

Do you have any citation on Thymosin and MS that I can take a look at?

[@ramazan9857]

When will remyelination treatment arrive?

[@rizayoruk3788]

Maybe one day

[@paul6150]

Really someting special they are going after progressive ms patients that do not respond to DMT. Would love to be in the EMBOLD study but, New York is a 7 to 8 hour flight and the first year 23 visits are required. Besides that i bet about every patient with progressive ms in the USA is signing up for this one. New numbers from the phase 1 are going to be released this quarter right? Excellent video as always 👌

[@ericmcdonald377]

Thank you! Would you consider making a video on ms and melatonin, sleep cycle disruption, etc. It looks like melatonin may play a role in ms development and regulation. I’d enjoy understanding it better.

[@NestingInNashville]

I get enough sleep generally, but it just doesn't feel restorative.

[@MrKoshnica]

completely wrong subtitles :(

[@euenfheiejrj]

I have ms and don’t have ebv exposure per my blood tests.

[@emreberberrr]

I didnt understand why they test the disability improvement. I think prevent the worsening and stabilize the illnes are very good targets also. Please correct me if İm wrong but as I knoe there is no alternative treatment option available today which keep stable people with progressive ms. On the other hand, do we have any information or idea on why other persons make the same improvement? Can is there be a dosing problem? Do you have any ideal?

[@MrGedd85]

Dr. Beaber, I wrote a few earlier comments on this, not sure if they were deleted or that they did not appear. I read the article in New Scientist regarding the EBV study on a large military subset of data that showed significant correlation and causation between MS and EBV. My question is that with this study being so conclusive, does this mean that, if it is safe for an inidividual to do so, that they should be now considering the high efficacy options for B cell depletion as the best way to manage the disease until something more targeted for EBV (such as the ATA 188 you describe in this video) comes along. For example, does this now mean drugs such as Tecfidera should only really be considered where a high efficacy option such as Ocrevus is not safe or appropriate for that patient? (I appreciate you can’t give medical advice here, but I would value your opinion on just how much a step change this study is going to provoke within the MS community inn terms of approach to treatment available now, and the direction of research towards EBV) Lastly, will an ‘antiretroviral’ such as one might take with HIV be developed for those with MS for EBV infected B cells? Appreciate the insight, and enjoy your videos. Many thanks.

[@DrBrandonBeaber]

In general, I believe that high-efficacy disease modifying therapy will on the average produce better long term results than low-efficacy disease modifying therapy.

[@lighto999]

It worked in 9/25 pts. wonder why the majority had no efficacy?

[@Py16777216]

This is extremely intresting. I have MS but I'm unsure about the EBV however if it is is the root cause of MS I'd be willing to take it as a treatment especially if you only have to for a few years until the virus is undetectable. One infusion trageting a virus per year would be desirable if it has comparable efficacy to drugs like Ocrevus.

[@RobertGabbert-j3r]

I've been on the study for a year with ATA 188 I had big hopes for best treatment but I have discovered that first year it's been nothing but a placebo I'm starting in my second phase Ada 188 my understanding is that I will start getting the grill medicine really upsetting disappointing to find out that first year has not been the real medication

[@DrBrandonBeaber]

That is disappointing, but thank you for entering the trial and taking the risk of getting the placebo, no doubt helping get us valuable data for the benefit of future generations of people with MS

[@cazleealleycat]

I recently read a moderately technical but dumbed down for a not-a-doctor reader book that aligned with my moderate understanding of medicine and the immune system and this was very interesting from an immune perspective. I'm a woman with SPMS and I'm definitely interested in learning more about this. I'm on ocrevus personally and I dont feel like its doing much for me. My chief complaints led my neuro to believe I might be dealing with NMO and its not entirely ruled out yet which complicates things though.

[@DrBrandonBeaber]

Generally speaking, NMO is a relapsing disease and only very rarely has been reported to cause slow progression. I would imagine ocrevus would be effective for preventing NMO relapses (given the success of rituximab in this disorder). Best of luck in your search for answers.

[@cazleealleycat]

@@DrBrandonBeaber yep, thats what my neuro explained, my diagnosing MRI leans both ways based on the way my spine lesions look if I remember correctly on why he hasn't ruled NMO out yet. So he went with "officially SPMS to get you on a DMD, but need to continue to evaluate". I'm hoping we'll get a better insight into how well Ocrevus is helping with a follow up MRI the next couple of years. My first half dose of Ocrevus was the first week of January of 2020. My Dr has rathered to hold off on additional MRI's due to the world at large especially since I haven't had a major relapse. We're incredibly fortunate medications to help manage these conditions. Along with awesome doctors to help us learn about what we're up against! I really appreciate how much I've learned from your videos.

[@cazleealleycat]

I wanted to clarify since it might sound like an odd decision to jump to SPMS like that. I didnt meet diagnostic criteria, until all of the sudden I did. Through the past 15 years from when I went through CIS, my main symptom was optic neuritis. My right eye would flare up every couple of years without significant MRI findings til suddenly I went numb from my ribs down on my right side, and that lead to the imaging study where we found the lesions in my thoracic spine, and lesions turned up in my brain as well with that study. The jump straight to it was based on the history of symptoms, documented progressive deterioriation of visual field tests and how the flare that lead to the diagnosis behaved and the symptoms that persist after that major flare. I had been in a bad car wreck shortly before the first CIS with ON so other physical symptoms were justifiably treated with caution in order to avoid a misdiagnosis. My neuros over the years have been cautious to not hear hooves and think zebras, as the saying goes. The draw back being obviously the seemingly quick transition once my current neuro got his arms around the flare that led to diagnosis and we were able to get copies of previous neuros & neuroophthalmologists charting and build a complete history.

[@arr2820]

What caused you relapse?

[@cazleealleycat]

@@arr2820 It's hard to say. If I had to guess I think it was a combination of having a very young child stress, work stress, my immune system being under stress from repeated illness from my kid bringing every bug from daycare home, and bad luck. I hadn't had substantial symptoms for about 2.5 years prior to the relapse that led to my diagnosis.

[@DrSheaBA]

Doesn’t most of the population have exposure to EBV? How can they tease apart/isolate them to show causation?

[@andresrodrl]

Looking if they are evb positive at the time of diagnosis

[@DrBrandonBeaber]

It is not 100% proven, but the fact that EBV negative MS is extremely rare and the timing of seroconversion prior to clinical MS strongly suggests a causal link.

[@yoanadimitrova8760]

It doesn't make any sense, 98% of controls have ebv vs 100% of people with MS, I like you doubt this is significant. Antibodies show recent exposure anyway and might not be detected at low levels.

[@yoanadimitrova8760]

@@DrBrandonBeaber so ebv negative ms does occur lol combined with 98%+ of controls being seropositive it makes this a hypothesis that doesn't even make sense, let alone be "proven" as you call it

[@DrBrandonBeaber]

@@yoanadimitrova8760 Background seroprevalence in the general population in the US 82.9% (80.0%-85.9%) among 18-19-year-olds according to this study: www.ncbi.nlm.nih.gov/pmc/articles/PMC3661547/#:~:text=The%20overall%20seroprevalence%20of%20Epstein,%2D19%2Dyear%2Dolds. It rises with age. For more information about EBV and MS, take a look at this video: kzbin.info/www/bejne/pKrGenutmbypY9k

[@97kuba1997]

are there any studies that say that taking acyclovir can help patients with PPMS? could it be helpful? my mother has this condition and is disqualified from taking ocrelizumab

[@barbaradascalos4411]

Think ACV only helps shingles..EBV has no drugs to control it. For chronic active EBV only real treatment is hsct.

[@dleufven6308]

Dr. Beaber, if ATA188 or Masitinib is approved in 2 or 3 years, will B-cell depletion or immune system suppression/damage from repeated use of Ocrevus, or Ocrevus replaced by Mavenclad or Lemtrada, limit the effectiveness of new therapies that treat the immune system and living (but undesirable) B cells in a different way?

[@DrBrandonBeaber]

I honestly don't know the answer to this, but it's an important question to ask. This might not be parsed out for several years after approval.

[@janehouska224]

Glad to see this information about the ATA-188 study! My neurologist enrolled me for this study however I was not eligible to participate as I had a melanoma removed about 10-15 years ago. The more I find out about the study, the more I am so disappointed that I could not participate. I a currently on Ocrevus (4 yrs) and it does not seem to be working that great for me. Curious why the melanoma disqualified me from the study. Any ideas??? I hope that if/when this treatment becomes available, I will be able to get it! Thanks again!

[@DrBrandonBeaber]

Unfortunately, history of cancer is often part of the exclusion criteria because the investigators fear a cancer recurrence (even if coincidental) could end up souring the safety data.

[@janehouska224]

@@DrBrandonBeaber appreciate your response. Thanks for this You Tube and all your other You Tube postings. I Learn so much from them and also Aaron Boster You Tube postings. You guys are good, professional and credible with the information you share . Greatly valued and appreciated!!!

[@wadejensik651]

Very interesting!!!!! Had EBV first now they say its Ppms 🤷🏼

[@mary-vy3mo]

stock is at zero...company stops trial..does not work

[@DrBrandonBeaber]

very unfortunate

[@relledom]

Dr. Beaber, thank you again for this exciting piece of news. What about Natallizumab = Tysabri affecting B cells? I thought that it was not targeting B-cells, or am I mistaken? I had a talk with my neurologist just yesterday and he was not really excited about the EBV MS study in Science. Maybe studies like the one you have presented here will make him more excited. :) Greetings from Germany! :-) PS: Should you be visiting Germany one day just contact me and I can, depending on where you will be, invite you to a coffee and show you around. :-)

[@DrBrandonBeaber]

Natalizumab does not deplete b-cells, but it prevents them from entering the central nervous system. I have never been to Germany, but perhaps I will be there someday for ECTRIMS. :)

[@charlespatton4470]

Dr. Beaver have you seen the recent journal from Harvard about EBV and MS? Just last week. Would love a video or comments on the study! Thanks for all you do!

[@DrBrandonBeaber]

I am going to do a video on this shortly

[@charlespatton4470]

@@DrBrandonBeaber awesome!!! I so look forward to it. Seems promising but I want to hear your thoughts

[@jasonc5289]

I didn't add this to my last post because I want it seen. The World Health Organization rated us 37th. The study I like, however, is from 2017 where we rank 54th, with Macecdonia barely, and I'm talking BARELY, in 55th. You should feel so ashamed of yourself. Terribly ashamed. My Uncle has MS and he didn't have to go through what he's been through. Again, you should feel so ashamed. I'm trying to wrap my mind around this. So many thank you - for what? Making people take a drug that that have no need to take. None. And in America they're just now admitting to the real cause of MS? Really? It's 2022. The gig is up.

[@user-xk3lj3sc5p]

Sounds very exciting! Question though, you mention EBV hanging around. I had mono in HS. A very very very long time ago. None of the MS treatments have worked for me. This past October my teen daughter was diagnosed with Mono. Both of us were stricken with the severe fatigue, & my MS symptoms all of a sudden were raging mad! Can mono (ebv) reactivate in someone if they are re-exposed or perhaps they were harboring there all along & then just decided to explode on me again?

[@SaraC-us5ky]

Happened to me every time I’ve been exposed to herpes virus! Like: herpetic hencephalitis and shingles!!

[@user-xk3lj3sc5p]

@@SaraC-us5ky thanks for your response. I have asked this question over and over. No one has answered... so I assumed no one knew.

[@hotpastrami]

When and how will ATA 188 be made available in Europe? Is there a study profile available to reference for the contact information of participating Practitioners? Is Michael Pender still involved or is entirely organized by Atara Bio?

[@DrBrandonBeaber]

I only see US and Australia sites available on the clinicaltrials.gov site right now. You can contact the Study Director at 650-278-8930 ext option 1 or by e-mailing [e-mail] clinicaltrials.gov/ct2/show/NCT03283826 I don't know if Michael Pender is involved.

[@SaraC-us5ky]

I have a couple more questions: - would an HBV vaccine would protect non exposed people? Or the virus would colonize anyway considering also vaccinated people can still have shingles? - is there any other drug or antiviral that may keep HBV under control? What about ivermectin?

[@karindella]

What about Tysabri?

[@jessicaisnetto9935]

In theory if EBV chronically effects the B cells in PWMS would their IGM still be positive for EBV even years after exposure?

[@DrBrandonBeaber]

I'm not exactly sure what you mean, but the IgM does not stay positive.

[@rmakids]

Tysabri is highly effective and does not destroy b-cells.

[@DrBrandonBeaber]

true, but it sequesters b-cells outside of the central nervous system.

[@lindavanzwol2643]

In a facebook group of MS patients,one woman said she has MS, but was negativ on EBV. ( She just had aHSCT, so the proof might be just in her medical files) ....so i severly DOUBT the effectiveness of this new thing. Also the fact that its the new hot thing everybody talks about, smells like big pharma funding.

[@quantumdecoherence1289]

I'm unclear , with the PPMS subject at 10:19, 56/F who had an improvement of her EDSS from 4.5 to 3.0, how this doesn't translate at all to any significant decrease in T25F test. So did just her hand function improve? I believe that, as my comment below states, that in PPMS and SPMS, axons have already been damaged and stopping the virus from causing further neurodegeneration/inflammation will be too late to reverse established disability.

[@DrBrandonBeaber]

Some people with progressive MS can experience reversal of disability. The underlying pathophysiologic mechanisms behind this are unclear.

[@quantumdecoherence1289]

Thank you for the reply Dr. Beaber. It is interesting that some patients have reversal and others do not respond as well. It appears that the higher the EDSS at baseline, the less improvement of function we see possibly due to the reduced reserve capacity of the CNS for repair.

[@arr2820]

@@DrBrandonBeaber have you heard about edss over time table for prognosing ms behaviour? Is it true?

[@DrBrandonBeaber]

@@arr2820 I'm not sure what you mean about prognosis but I do have a video explaining EDSS: kzbin.info/www/bejne/rGrWd5yDlNGegJY

[@aalihte3378]

How does a doctor determine what type of Ms you have?

[@DrBrandonBeaber]

I have a video on subtypes which should answer this questions for you: kzbin.info/www/bejne/aIXZhql3Ysmsjqc

[@Alan01]

Couldn't the improved walking speeds be a placebo effect of being in an open label study? They don't large enough to me.

[@DrBrandonBeaber]

Sure. We will see what the EMBOLD study shows.

[@desiredecove5815]

Thank you for touching upon this #sharingiscaring

[@demoskunk]

Is ATA 188 more effective than Tolebrutinib, so far?

[@DrBrandonBeaber]

There is no way for me to answer this because we don't even know if it is effective.

[@barbaradascalos4411]

The new is starting to come out..seems at best ATA 188 just stabilizes disease and does not improve edss..search "no news atara"

[@NestingInNashville]

I failed out of the ATA188 trial several months ago. I have SPMS and had to withdraw from the trial due to progression. Of course, I may have been on placebo...

[@matiouz07]

You should have stay in, if you was on y1 placebo arm, the y2 you switch to ata188. Ata 188 is given to any participant in open label extension of the embold study.

[@NestingInNashville]

@@matiouz07 I considered it but I was only 3 or 4 months in and I lost several, several minutes on my timed walk. I needed to stabilize on a DMT and I have.

[@petergeddis4656]

Not sure why my comment was removed?

[@arr2820]

It can not be accelerated. You have to wait and see to learn about long term effects

[@Joe-gw2pb]

I go to Penn in Philly. They had 4 spots for the trial. Tried but wasn’t accepted. PPMS they gave me an edss of 6.5 38 at the time.

[@DrBrandonBeaber]

:( You still could potentially be a good candidate for the treatment if it is proven effective in the future.

[@NestingInNashville]

I failed out of the ATA188 trial several months ago. I have SPMS and had to withdraw from the trial due to progression. Of course, I may have been on placebo...

[@DrBrandonBeaber]

@@NestingInNashville :( Let us know when you get unblinded.

[@powmowwow]

In theory it should be effective in all MS patients? If EBV is associated with causing/progressing MS, wouldn't we want to see all patients get better? Would patients with RRMS have to wait for another trial to finish up?

[@DrBrandonBeaber]

This is an interesting question. I don't know exactly when they plan to start an RRMS trial.

[@arr2820]

What if some people have EBV but never been diagnosed with Ms since not having any symptoms, will they be chosen as healthy donors(even if they have "ms sleeping in their body")?

[@DrBrandonBeaber]

@@arr2820 I don't know the technical details about how they would select and process the samples.

[@rathernotsay5629]

I have not had any contact with the virus other than being vaccinated for mono in my childhood. (thoughtfully scratching head)

[@lush462]

Before there was no vaccine for EBV. Moderna is now testing an mrna ebv vaccine in phase1

[@arr2820]

First phase of trial was successfull)

[@zoranagavrilovic9403]

Exciting!

[@henp99]

❤ Posted this videoh and said please God?

[@dominicp134]

all not working yet, Coimbra Protokoll is the answer , remission for lesions. Stem cell therapy too expensive, better to treat the people with aspirin, also here in europe

[@arr2820]

Are you on coimbra protocol?

[@Skypods1]

you mean 😢 I can finally play sports with my children? 15 yrs still in the trenches!

[@GabrielPerez-dk2re]

Can they accelerate the trial as in Covid19? I mean the procedure. I think that patients will appreciate that.

[@klzeller]

This is going to cost a fortune. Oh well...