BC007 - what are your thoughts?

[elvira]

Hello!

With studies for Long Covid and ME/CFS with the drug BC007 starting this summer, I was wondering what people’s thoughts are of the outcome. How much will it help for Long Covid respectively ME/CFS? Is it something to hope for? Please share whatever you’re thinking 🤗

Cheers! (Tagging some people that might know something - @Martin aka paused||M.E. @Pyrrhus @Hip )

 

[RL_sparky]

Comment from a novice here. I'm excited to see this trial. If autoantibodies are involved and patients get better
this would be a huge leap in our understanding of what is driving this disease.

 

[elvira]

Comment from a novice here. I'm excited to see this trial. If autoantibodies are involved and patients get better
this would be a huge leap in our understanding of what is driving this disease.

Thank you for your thoughts! I’m also excited, I really hope for some good results🙏

 

[elvira]

I’m a bit confused since Carmen Scheibenbogen say that 30% of ME-patients have these autoantibodies, while OMF has a swedish study where they found them in 70%. Apparently 90% of Long Covid patients have them. Even if one have them, it’s hard to know how much damage they do and how much of ones symtoms have other causes...

 

[vision blue]

Skeptical but curious

So for instance, the anectdote tthat gets solited alot of the 59 year old man says he felt better from long covid symptoms within hours of the first iv treatment. If The drug is supposed to bind auto antibodies, which is I believe what it’s supposed to do, should it make a person feel better that fast? Auto antibodies usually set in motion a slower process involving cytokines (siri transcribed this as Seidel Keynes!) and inflammation and so on and even if you get rid of all the antibodies I would think it would take a while before the effects of the previous damage faded, certainly more than hours But I could be wrong Perhaps also its a different feature of the drug that lead to at least the first wave of feeling better

Do you a citation on the glaucoma and auto antibodies and use of the drug to treat that? I like I might get some more basic info on the rug and mechanisms by looking at that work but I have not found it yet.

In othervwork i do know of finding that SSA autoantibody found on normal pressure glaucoma but thats a different antibody Also dont know what kind of glaucoma the resesrchers first thought thid drug would be good for.

Also havent looked up
Yet how this drug binds to autoantobidies or how the drug increases blood flow

Ive seen one article of theirs in frontiers in ophthalmology but be warned frontiers journals these days are considered predatory journals.

In general, i would t be surprised if alot of viruses affect vasculature.

 

[ruben]

Just read on Twitter that first "long covid" patient to receive BC007 drug says he is pretty much his old self.

 

[Dude]

Just read on Twitter that first "long covid" patient to receive BC007 drug says he is pretty much his old self.

I follow him on Facebook, he just wrote he went 2h Wakeboarding without any problems, about a month ago he was considering to buy a wheelchair. Boy the hopium is real. I really hope this is the one size fits all magic pill we are all waiting for.

 

[BrightCandle]

The Trial is hyper focussed on those with detected GCPR antibodies. This will likely mean treatment is similarly limited too if it gets approved.

 

[Dude]

The Trial is hyper focussed on those with detected GCPR antibodies. This will likely mean treatment is similarly limited too if it gets approved.

I partially agree with you, but the question still remains whether the antibodies measured actually play a major role.
The mechanism of the drug is still poorly understood. As described here:
https://www.kinder-verstehen.de/wp-content/uploads/BC007_miracle_in_need_of_explanation_141221.pdf

I remember the discussions from the Facebook group, where countless people had these antibodies tested and sometimes had different results in the same laboratory. I think even Scheibenbogen (dont quote me on that) once said that these can also be elevated in "healthy" people. Part of the problem was that Berlin Cures probably used bioassay in the study (more precisely) while the other laboratories tested with Elisa. It is clear that they are very strict for the approval phase, as they want to suceed, but whether they really value giving the drug only to those who also have these antibodies after successful approval? I dare doubt, since it is not in the sense of their turnover.

 

[Osaca]

Since the trial studies the drugs effects on the patient as well as the functionality of various GPCR-AABs before during and after treatment as well as their correlation to symptoms, those questions will hopefully all be adressed once we have the trial results. Personally, I wouldn't worry about this at all. Everything depends on the trial results and let's be reminded that trials fail far more often than they don't, even more so for diseases for which biomarkers don't exist.

 

[Mouse girl]

the only 007 I've ever heard of is: Bond, James Bond. que music. sorry just had to.

 

[Mouse girl]

But seriously, never heard of such a thing.

 

[Dude]

the only 007 I've ever heard of is: Bond, James Bond. que music. sorry just had to.

But seriously, never heard of such a thing.

From all the Drug Trails going on right now, this is (imo) the most promising one.
Here is a good link to start with:
https://www.healthrising.org/blog/2...in-cures-long-covid-chronic-fatigue-syndrome/

 

[datadragon]

Its certainly helpful to be able to target areas like that to reverse negative effects of certain autoantibodies as needed and will wait for results of trials since they arent sure if its even the effect on autoantibodies that is what is being helpful, I should mention that butyrate which is found low in ME/CFS is a HDAC inhibitor. According to research, changes in short chain fatty acids profile after inflammation/infection is capable to cause the dysregulated antibody responses leading to generation of autoantibodies among many other downstream effects of the inflammation cascade. By altering chromatin accessibility, HDAC inhibitors alter gene expression. HDAC inhibitors butyrate, and propionate epigenetic modifiers exert modulatory effects on intrinsic B cell functions even at moderate concentrations, thereby is what shapes normal and effective antibody and autoantibody responses. Valproic Acid as well which only targets Class I (HDAC1–3 and 8) and Class IIa (HDAC4–5, 7 and 9) HDACs. Autoantibodies are found in healthy individuals, they arent all 'bad' but are being dysregulated in certain cases. The understanding and reversal of this process is the key as autoantibody-mediated autoimmune diseases are numerous and induce pathology by a variety of mechanisms https://www.frontiersin.org/articles/10.3389/fimmu.2017.00603/full

Advanced research:
Butyrate and propionate - SCFA histone deacetylase (HDAC) inhibitors (HDIs) play an important role in preventing or dampening dysregulated antibody responses, which can lead to generation of autoantibodies or allergic IgE, while maintaining a certain level of protective antibodies against microbial pathogens. The “safeguard” function of SCFAs in dampening antibody overproduction and preventing emergence of autoantibodies which is helpful was also shown that it can be reversed by estrogen which reverses the SCFA HDI-mediated downregulation of AID expression (AID, encoded by Aicda in mice and AICDA in humans) and CSR through selective modulation of miR-26a, This may provide (one part of) an explanation for the female bias in autoantibody-mediated autoimmune diseases, such as lupus, and the greatly increased incidence of food allergies in female adults.

The expression of Aicda- or Prdm1-targeting miRNAs can be modulated by histone deacetylase (HDAC) inhibitors (HDIs), including short-chain fatty acids (SCFAs) butyrate and propionate, which alter histone acetylation in the host genes of these miRNAs. By altering chromatin accessibility, HDIs alter gene expression. HDI valproic acid, butyrate, and propionate epigenetic modifiers exert modulatory effects on intrinsic B cell functions even at moderate concentrations, thereby shaping effective antibody and autoantibody responses. As epigenetic modifiers, SCFA HDIs inhibit Aicda expression and CSR through upregulation of select B cell miRNAs that silence Aicda, including miR-26a and miR-125a, in antibody and autoantibody responses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105609/

 

[ruben]

As I said on Twitter, maybe as I got glandular fever in summer 1972 and haven't been well since, perhaps I should be an early "guinea pig" for the BC007 drug. I would have thought if it works for me it can work for anyone.

 

[Dude]

Good explanation about Elisa vs. Functional assays GPCR testing.

The only ones who actually tested functional were probably Berlin Cures. But they stopped after the studies started. Also explains why so many are rejected, the other tests just aren't that meaningful i guess. I also did a test (Elisa) and had two at risk (B2, M3).
I would actually like to see a trial on an LC/MECFS patient with no elevated aabs, but i guess we have to wait till Q2-2024 for further knowledge. The tension is killing me

 

[Osaca]

I don't think that we can currently say that any of the tests are meaningful or not meaningful, they are all not comparable and not standardised, from measurement values to sex, age, weight, height, illness duration etc. There is no comparison on functionaliy of rat hearts in petri dishes vs human functionality and all of the test methods are heavily understudied. Perhaps they are all worthless, perhaps not. Finally all of these tests are only considering blood samples, which might not be reflecting what's happening elsewhere (luckily they haven't been found in the CSF) or what is already binding at receptors. However, Berlin Cures and other researchers are more than aware of these things and they will have chosen methods which they deem most favourable to achieve a positive outcome.

 

[Dude]

@Osaca i agree with you, i do believe they play a major role, but measuring seems quite a bit of a challenge. I've already thought the same thing, what if they aren't that easy to evaluate? So they are bound and cause problems, but cannot be determined by a simple blood test?
Another consideration of mine is, if there are actually people who don't have aabs and then the drug doesn't work, would that mean, that we have two groups of ME patients? I actually find this very unlikely (but possible). I mean, what are the odds if you have covid or EBV as a trigger and then it splits into two seperate illnesses with the same Symptoms?

I just found another chart with the MRNA Expression in PEM on these adrenergic and immun genes. Maybe another pointer?

PS: Sorry if i already annoy people with my endless discussions, but i do believe this might be the first therapy for MECFS. And iam bored as well

 

[Osaca]

@Osaca i agree with you, i do believe they play a major role, but measuring seems quite a bit of a challenge. I've already thought the same thing, what if they aren't that easy to evaluate? So they are bound and cause problems, but cannot be determined by a simple blood test?
Another consideration of mine is, if there are actually people who don't have aabs and then the drug doesn't work, would that mean, that we have two groups of ME patients? I actually find this very unlikely (but possible). I mean, what are the odds if you have covid or EBV as a trigger and then it splits into two seperate illnesses with the same Symptoms?

I actually believe that there will be multiple groups of diseases and it is extremely likely that there will even be very different diseases or disease categories and not everything that is nowadays considered to be ME/CFS will be so in the future. Even in MS, where biomarkers exist, there are different types of MS where different therapeutic pathways are trialled. ME/CFS would probably be the first time in medical history and as such, very unlikely, that broadly grouping patients together on symptomatic presentation would yield one definite group of patients with one disease mechanism. Just imagine MS wouldn't have a biomarker, then ME/CFS and MS patients would probably be lumped together and they probably won't have the same therapeutic cure.

I mean, what are the odds if you have covid or EBV as a trigger and then it splits into two seperate illnesses with the same Symptoms?

Very likely actually. Just look at all the different types of Long-Covid, they are certainly not all the same illness. For EBV it's even more complex. 95% of the world population are completely unaffected by it and then there is a small minority for which illnesses like ME/CFS, cancers and possibly other autoimmune diseases like MS might arise. If EBV can do all of that and ME/CFS in itself is already a tail event, then why shouldn't there be separate type of illnesses and events that EBV can trigger, that certainly doesn't seem unlikely?


Just based on probability it isn't likely that the IA trials and BC007 will be a success, but we're certainly hoping the opposite. A failure would definitely mean that the whole Scheibenbogen/Wirth hypothesis will have hit a road block, let's hope for the opposite, but I wouldn't bet a cent on it.

 

[Dude]

I actually believe that there will be multiple groups of diseases and it is extremely likely that there will even be very different diseases or disease categories and not everything that is nowadays considered to be ME/CFS will be so in the future. Even in MS, where biomarkers exist, there are different types of MS where different therapeutic pathways are trialled. ME/CFS would probably be the first time in medical history and as such, very unlikely, that broadly grouping patients together on symptomatic presentation would yield one definite group of patients with one disease mechanism. Just imagine MS wouldn't have a biomarker, then ME/CFS and MS patients would probably be lumped together and they probably won't have the same therapeutic cure.

That's not what I meant. Of course, depending on the damage, the expression of the disease can be different and of course there are then different groups, but to go back to your example, with MS, we know that the body's immune system attacks the central nervous system (brain and spinal cord). This leads to inflammation and damage to the protective covering around nerve fibers, and symptoms vary in severity depending on where this inflammation occurs. But the way the disease works, is always the same. What I mean by that is, if the cause is in some these autoantibodies, i dont find it likely that in another person, it is suddenly intestinal bacteria for example (if the trigger was the same virus). Lets exclude Long Covid, we know that it can be an umbrella term for different diseases such as organ damage, MECFS type, etc.
Again that's just my theory, but if these aabs play a major role, it think it will be the cause in the majority of MECFS. (exluding those with spinal cord problems)