As Carmen Scheibenbogen’s group was tracking down autoantibodies that affect the blood vessel functioning in chronic fatigue syndrome (ME/CFS), a small German group called Berlin Cures was using a different assay to assess the same autoantibodies in heart failure.
They had a drug called BC 007 that’s able to bind to and neutralize autoantibodies that attach to the G-protein-coupled receptors (GPCRs). Their 2016 paper claimed their new approach was easier and possibly more effective than past treatments such as immunoadsorption that have been used to mop up these autoantibodies.
Berlin Cures BC 007 Video
Several papers were then published which highlighted the new drugs’ potential usefulness in what the authors called the “functional autoantibody diseases” such as complex regional pain syndrome, postural orthostatic tachycardia syndrome, ME/CFS, and others. The papers again asserted that other means of removing these autoantibodies such as plasma exchange, immunoadsorption (which they agree can be effective), intravenous IgG treatment (IVIG), or Rituximab were either more costly, less effective, or more toxic than the BC 007 aptamer.
The BC 007 drug came to long COVID circuitously. Originally created to neutralize autoantibodies in autoimmune heart failure, the same autoantibodies were subsequently found in glaucoma, as well. When a patient with glaucoma who just happened also to have long COVID found that his long COVID symptoms cleared up after a single treatment of the BC 007 drug, the company looked deeper – and found one of the GPCR autoantibodies in long COVID.
Dr. Hohberger of the Erlangen Eye Clinic explained:
“Originally, I wanted to use it to help my glaucoma patients. When we then saw the results that arose from cooperation projects on Long COVID, it was like many small pieces of the puzzle that fit together for us. It was quite conceivable that the long COVID symptoms could also improve as a result. “
In November, Berlin Cures published a successful case report of that person. Since then, at least two more people with long COVID who have received the 75-minute infusion of the drug have reported rapid results. (All three patients were monitored in the hospital for three days after receiving the drug.)
One of them, a cross-country skier and former iron man participant (!) was clearly in superb shape before getting the whole, dreary long-COVID package. Months after the infection, he stated:
‘I was completely disoriented and unfocused, I was just trying my best to survive from one day to the next. I was a shadow of my former self, a zombie. I barely recognized myself.’
“I was no longer able to follow conversations, I couldn’t draft a presentation or carry out negotiations and my colleagues had to help me with everything. At home, tackling the smallest chores became a major challenge, and for a while, I even needed at-home help. Reading, pottering around in the garden, or taking my dog for a walk was basically all I could cope with. As if that wasn’t enough, I was plagued by financial worries, panic attacks, and what I call emotional incontinence. I was completely incapable of keeping my emotions in check.’
The week following the injection, everything – his physical and cognitive abilities and emotional balance returned.
The next long-COVID patient – also an avid exerciser – was bedridden, experienced temporary bouts of paralysis, could not follow conversations, etc. She did not experience a complete recovery but her symptoms improved markedly.
The autoantibodies in question quickly decreased after the treatment and stayed that way for the next month. The improvements seemed to stick, as well, lasting at least several months.
Small Blood Vessels in the Eyes Affected
Berlin Cures believes the drug is soaking up autoantibodies that are interfering with the microcirculation. Led by Dr. Hohberger, researchers have determined that blood flows to the eyes in COVID-19 and long COVID are diminished even in patients without any visual problems. They’ve even been able to identify the most impacted microvascular layer in the retina that’s been affected. They reported:
“These results argue for a critical impairment of retinal microcirculation after COVID-19 infection, accented in the ICP, yet affecting additional adjacent microvascular layers after even worse COVID-19 infections.”
As others have, they proposed that the SARS-CoV-2 coronavirus’s entry via the ACE-2 receptor into the endothelial cells was causing the problem – and they cited sepsis as a possible model. As the virus entered the cells, it sparked a hypercoagulation response which produced microclots. They also hypothesized that the capillary damage they’d seen in the eyes simply reflected a massive disruption of the small blood vessels across the body.
“We hypothesize that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation.”
A recent review of “retinal micro-vasculopathy” (damage to the small blood vessels in the eyes) due to COVID-19 reported that despite the numerous issues found (“cotton wool spots”, microhemorrhages, and venous tortuosity), the problems found, thus far, are mostly “subclinical”; i.e. not causing impairments in vision.
Clinical Trial Soon to Get Underway
Word about the successes quickly got around prompting Berlin Cures to state that “Since our first therapeutic successes became public, we have received countless inquiries from those affected.” They stated that no further attempts to use the drug to treat long-COVID will be made until a drug trial has been completed.
Thankfully, the German government stepped in to fund a small trial of BC 007 which led the researchers to report: “we now have the opportunity to decisively advance our research in this important area.”
Three groups – The Erlangen Eye Clinic, the Max Planck Institute, the Humboldt University in Berlin and the Helmholtz Center in Munich – appear to be working together to figure out what’s what with the drug and long COVID. The clinical trial will start in 2022 and is expected to last for the next year and a half.
People with long Covid who are interested in the trial can contact Erlangen University Hospital at email@example.com You’ll be contacted regarding trial eligibility, dates, etc.
Will the “German Miracle” Work for ME/CFS?
- Originally developed to treat autoimmune heart failure, the BC 007 drug targets the same autoantibodies under question in ME/CFS, It also is apparently easier and cheaper to administer than the immunoadsorption technique that’s been trialed in ME/CFS.
- When one of those autoantibodies was found in a long-COVID patient with glaucoma, the drug was tried – and resulted in a long-COVID recovery. Since then, several other long-COVID patients have either rapidly recovered or significantly improved, and the recoveries appear to have stuck for at least several months.
- The drug also cleared up microvascular damage in the retina of the eyes and dramatically reduced the elevations of the autoantibodies in question. The authors believe the microcirculatory problems in the eyes may exist in the rest of the body as well.
- The microvascular problems in the eyes are intriguing as small fiber neuropathy has also been found in the eyes of ME/CFS and FM patients, and small fiber neuropathy can affect blood circulation.
- A small German clinical trial is assessing the effectiveness of BC OO7 in long COVID. German research groups are also attempting to learn how BC 007 is doing what it’s doing in long COVID.
- Other means of mopping up autoantibodies are available. Two small clinical trials suggest that immunoadsorption may be helpful in some people with ME/CFS, and a group of mostly German researchers has called for the use of apheresis in ME/CFS.
Dr. Renz-Polster suggested that increased brain blood flows may not only cause a rapid improvement of brain function but may be able to quickly “abolish the inflammatory milieu which may be at the root of the clonal B-cell expansion and the Aab (autoantibody) production.”
Alternatively, the increased blood flows may be able to reset the sympathetic nervous system -thus abolishing the immune activation it had provoked. The drug may, also, by restoring normal Ang II activity, repair cardiovascular functioning, turn off inflammation, restore brain functioning, and others. Plus, there’s more! Check them out in Dr. Renz-Polster’s paper. (Thanks to Dr Renz-Polster, Brenden, Jutta, Fritz, and others for links and information regarding BC 007.)
Deformed Red Blood Cells as Well?
An Erlangen research team from the Max Planck Institute for Physics and Medicine and the German Center for Immunotherapy has found evidence of deformed red blood cells that they believe are inhibiting oxygen supplies to the tissues in long COVID.
Like Ron Davis, the Erlangen research team has apparently developed their own method – called “deformation cytometry” – to assess the red blood cells in long-COVID patients. They hope to produce a “fast, reliable and inexpensive” diagnostic technique” for long COVID.
The red blood cell deformability finding suggests the blood could be blocked from reaching the tissues in multiple ways (deformed red blood cells, narrowed blood vessels) in long COVID and possibly ME/CFS. Given the degree of disability sometimes found in these diseases, the possibility that multiple harms to the blood circulation system exist doesn’t seem surprising at all. Whatever is happening is having a profound effect. One study, for instance, found that ME/CFS is significantly more functionally debilitating than heart failure, type II diabetes, or multiple sclerosis.
Whether or not the deformed red blood cells are being affected by the autoantibodies isn’t clear, but it’s possible that autoantibody-induced endothelial cell dysfunction could be creating enough inflammation and oxidative stress to cause the damage. Ron Davis has been digging deeper and deeper into the deformed red blood cell issue in ME/CFS and the Open Medicine Foundation recently announced a new grant to study them. Find out more about that work here.
Small Nerve Fiber Connection?
The microvascular retina findings bring to mind the small fiber neuropathy (small nerve fiber damage) findings also found in the eyes of people with ME/CFS and fibromyalgia. Like the microvascular issues, the small fiber neuropathy findings in the eyes don’t seem to be causing much mischief. Like the microvascular findings, though, small fiber neuropathy findings in the eyes and/or skin of fibromyalgia, ME/CFS, POTS, and long-COVID patients have been proposed to reflect systemwide issues.
For instance, Systrom has proposed that small nerve fiber damage is shunting blood away from the capillaries in the muscles. It’s possible, then, small nerve fiber damage might be associated with microcirculatory issues in these diseases. Small nerve fiber damage has been associated with microcirculatory problems in other diseases such as diabetes and chemotherapy-treated cancers.
If it’s true that small nerve damage is contributing to the microcirculatory issues in ME/CFS, FM, etc. we’ll need to know just how important those microcirculatory problems are, what’s causing the small nerve damage in the first place, and how the small nerve fiber damage in ME/CFS differs from that found in other diseases.
Other Autoantibody Treatments
Immunoadsorption is another technique that’s been shown to mop up autoantibodies. In immunoadsorption, blood from the patient is run into a machine that filters out certain portions – such as autoantibodies – from it. A couple of small studies have produced mixed results in ME/CFS.
A small 2018 study found that a 5-day treatment regimen resulted in dramatic reductions in autoantibody issues and improved endothelial functioning. Seven of the 10 patients reported a rapid improvement of their symptoms which lasted for 6-12+ months. None of the patients recovered, however, and despite an improvement of other symptoms, five reported a worsening of fatigue towards the end of the trial.
Two years later a repeat trial in five of the responding patients was done. As in the first study, autoantibody levels dropped dramatically. Two of the patients reported a significant improvement in their fatigue, while two others reported only a small improvement in their fatigue but improvements in other symptoms. One person got worse.
A mostly German group of researchers has been championing the idea of using extracorporeal apheresis in ME/CFS and long COVID. In apheresis, portions of the blood are removed from the patient and then filtered.
They reported that their clinical observations suggest that extracorporeal apheresis used over either 2 or 4 days can significantly improve symptoms. ME/CFS patients with a clear-cut history of infectious onset seemed to do best, and they found elevations of autoantibodies to neurotransmitter receptors.
While apheresis is effective in reducing antibody levels, the authors also noted that because it may affect other parts of the immune system, that exactly what it’s doing is unclear.
IVIG is another possibility that will be covered in another blog.
Once again, we see the interest in long COVID pop out another treatment possibility for ME/CFS and related diseases.
The BC 007 drug is certainly an intriguing compound. Originally developed to treat autoimmune heart failure, the drug targets the same autoantibodies under question in ME/CFS. Apparently easier and cheaper to administer than some other options, the drug developers have had their eyes on diseases like ME/CFS and postural orthostatic tachycardia syndrome for quite some time.
When a person with both long COVID and glaucoma recovered from long COVID following getting the drug, test results revealed he had an autoantibody the drug was able to mop up.
The drug’s results in a few long-COVID patients were impressive, with some patients fully recovering. Test results showed a rapid reduction in their autoantibodies and an improvement in their retinal microcirculation. The damage found in the microvascular regions of the retina was intriguing given the findings of small fiber neuropathy in ME/CFS, and FM patients’ eyes. The German government is funding a small clinical trial in BC 007 and long COVID.
Other ways to mop up autoantibodies are available. Immunoadsorption has produced some positive results in a few small treatment trials in chronic fatigue syndrome, and apheresis is being championed by another German research group for the treatment of ME/CFS. IVIG and drugs like rituximab provide other possibilities.
BIG (little) Drive Update!
Thanks to the over 170 people who have supported Health Rising, our year-end fundraising drive is roaring along.
Health Rising is fixated on possible treatment options. Over the past six months we’ve covered six long COVID treatments that have popped up (BC 007, stellate ganglion blocks, Bruce Patterson’s statins, AXA1125, inspiritol, oxaloacetate) and they are surely just the beginning. If keeping up on emerging treatment options for long COVID, ME/CFS, FM, and others makes your autoantibodies want to squeal and run for cover, please support us.