It can be shown in all of the mentioned diseases that autoantibodies bind to and stimulate certain cell surface receptors and imitate a non-existing chronic physiological stimulus with undesirable, pathologic and deleterious effects on the concerned organ (heart, nerve system, lung, eyes, kidney, etc.).
BC 007 is the only known compound capable of neutralizing functionally active but pathological autoantibodies directed against G protein-coupled receptors. There are a large number of diseases for the development and chronification of which, despite intensive research, no explanation can be found to date that are linked to positive humoral detection of these autoantibodies.
To name just a few, these are pulmonary hypertension, glaucoma, Chronic Fatigue Syndrome (CFS), and of course Long Covid and heart failure.
For heart failure, a direct causal relationship to the development and its maintenance can be discussed in that neutralization of autoantibodies leads to an improvement in cardiac function and significantly lower mortality in affected patients.
In patients with Long Covid, neutralization of the autoantibodies by BC 007 in compassionate use treatments could bring them to a state that could almost be described as a cure.
In contrast to simple destructive autoantibodies, so-called „functional autoantibodies“ perform a hormone-like function in the body and can lead to an imbalance of hormonal control for different organs. Gerd Wallukat discovered this subclass of autoantibodies and described them for the first time in scientific research papers as early as 1987.
These AABs have the special characteristic of stimulating cells via a highly specific signal pathway (so-called G protein-coupled receptors). Via these specific cell surface receptors, functional autoantibodies trigger their hormone-like function.
A group of scientists from the Max Delbrück Center (MDC), the Charité Berlin, and the German Heart Institute Berlin continued to study the significance of autoantibodies in heart failure and other autoimmune diseases for over 10 years. In the course of their research, it was detected that
the aptamer BC 007 was able to neutralize pathogenetic autoantibodies in the blood samples of patients.
Johannes Müller was the first to demonstrate the clinical significance of functional autoantibodies in a clinical trial (matched controlled study) at the German Heart Institute Berlin. Specifically, a pure mechanical method (immunoadsorption) was applied to purify the blood of 180 severely heart diseased patients from autoantibodies.
This led to an enormous survival advantage (lifespan extended in average 6.5 years).
However, despite the fact that the applied adsorption method, in general terms, was an extremely successful procedure to eliminate functional autoantibodies, the method was suboptimal as it proved to be expensive and medically complex and could thus not be established as a widely accepted method for the treatment of heart failure.
Driven by the medical success of autoantibody neutralization, a substance was sought that could replace immunoadsorption. After a series of failures, BC 007 – a non-modified 15mer single-strand DNA oligonucleotide; an aptamer – was found to be able to neutralize autoantibodies directed against G protein-coupled receptors.
Immediately after the incorporation of Berlin Cures, the preclinical phase I and phase IIa studies required for regulatory approval were initiated. In the preclinical and phase I studies, which have already been completed,
neither toxicity nor relevant side effects were found.In the Phase IIa, which is now ongoing, the good efficacy of BC 007 as a neutralizer of autoantibodies in patients with severe heart failure is being demonstrated.
and Clinical Studies
From 2015 onwards, extensive pre-clinical research and trials were followed by a large clinical phase I study in Germany in which healthy volunteers were subjected to increasing dosages of BC 007.
As this study could successfully be completed (no adverse side effect in any of the probands),a phase IIa-clinical study for the treatment of heart failure patients was initiated by Berlin Cures in late 2019.
This study will be fully completed in Q4 2022 and gives hope – so far impressive results are being achieved (average of 6% improvement of patients’ heart ejection, no adverse side effects). Already between 2016 and 2019, initial research was undertaken as to the potential curative effect of BC 007 in relation to Chronic Fatigue Syndrome (CFS), and glaucoma.
However, in early 2021, Berlin Cures’ scientists (in collaboration with other contributors) published the first research paper indicating that a series of patients previously infected with the Corona-virus contain functional autoantibodies targeting G protein-coupled receptors (i.e., autoantibodies targeting ß2- and α1-adrenoceptors, angiotensin II, AT1-, muscarinic M2-, MAS-, nociceptin- and ETA-receptors), actually proving the underlying cause of the Long Covid Syndrome (LCS).
In May 2021, researchers at the University Clinic Erlangen, Germany – in collaboration with Berlin Cures – started to apply BC 007 in compassionate use cases to four patients heavily suffering from the Long Covid Syndrome, i.e., with typical patterns of functional autoantibodies. The result was astounding: after a single infusion of BC 007 all patients completely recovered from the symptoms of Long Covid.
The goal of Berlin Cures, therefore, is to make BC 007 available on the market as fast as possible for LCS patients and, in parallel, to successfully complete all clinical studies for heart failure.
The status and progress in both fields are further explained in the section „BC 007 Pipeline“.
Before a patient is treated with BC 007 in a licensed clinic in the course of an approx. 75-minute infusion, a blood sample must be taken to determine whether there are actual signs of pathologic autoantibodies. After the treatment with BC 007, the neutralization of the autoantibodies must be shown in an analytic test.
To this end, Berlin Cures has developed and further improved a proprietary Bioassay (i.e., blood test) which reliably detects autoantibodies. This unique methodology, established as a „Gold Standard Test“ in bio-science, is basically the same for all diseases triggered by pathogenic autoantibodies (e.g., heart failure, LCS, etc.). It has been applied both in all phase I and phase IIa studies for heart failure and is now used for LCS cases.