Berlin Cures Patent for BC 007

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Berlin Cures Patent for BC 007

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The patent by Berlin Cures that describes the aptamer under consideration for treatment in Long Covid can be found here:

"APTAMERS FOR USE IN THE TREATMENT OF CORONAVIRIDAE INFECTIONS"
WO2021205012 (A1) ― 2021-10-14
https://worldwide.espacenet.com/publica ... cale=en_EP

"In a preferred embodiment of the second aspect, the disease symptoms comprise one or more from the group comprising neurological symptoms, such as chronic fatigue syndrome, postural orthostatic tachycardia syndrome (PoTS), dysautonomia, tremor, attention deficit, anomic aphasia, neuropathy, transverse myelitis, acute necrotising myelitis, and Guillain-Barre syndrome, cardiovascular symptoms, such as myocardial inflammation, arrhythmia, tachycardia, bradycardia, hypertension, and atrioventricular (AV) block, dermatological symptoms, such as alopecia and eczema, or gastrointestinal diseases.

In another preferred embodiment of the second aspect of the present invention, the aptamer is used to inhibit the interaction of autoantibodies specific for a G-protein coupled receptor with its target proteins.

In yet another preferred embodiment of the second aspect of the present invention, the aptamer is for use in the treatment of a patient in which autoantibodies against G-protein coupled receptors can be detected.

In one preferred embodiment of the second aspect of the present invention, the patient exhibits functional autoantibodies against G-protein coupled receptors, preferably functional autoantibodies specific for any one of the human G-protein coupled receptor adrenergic alpha-1 receptor, adrenergic beta-2 receptor, endothelin 1 ETA receptor, muscarinic M2receptor, angiotensin II AT1 receptor, MAS-receptor and/or the nociception receptor, more preferably for any one of the adrenergic beta-2 receptor, muscarinic M2receptor, angiotensin II AT1 receptor, MAS-receptor, particularly preferably wherein the patient exhibits an antibody pattern comprising functional autoantibodies specific for each of the adrenergic beta-2 receptor, muscarinic M2receptor, angiotensin II AT1 receptor, and MAS-receptor."

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"Two of the identified GPCR-fAABs, observed in over 90% of the investigated COVID-19 patient sera (23/25), were directed against receptors of RAS, namely the angiotensin II AT1 receptor and the angiotensin (1-7) MAS receptor. These vasoactive AT1-fAABs had been identified before in patients with malignant hypertension, therapy-resistant hypertension, preeclampsia, and kidney diseases."


PFPC Comment:

As mentioned already elsewhere on this site, angiotensin II AT1 receptor and the angiotensin (1-7) MAS receptor are coupled to Gq/11 (Canals et al., 2006; Cabana et al., 2015).

Numerous agents have been tried and tested to target Gq/11 pathways, namely the natural cyclic depsipeptides YM-254890 and FR900359, both of which are established as selective inhibitors of the Gq family (Tietze et al., 2019).

Zhang et al, in a recent paper (2020), also mentioned that "a peptide-based G protein antagonist-2A (GP-2A), a 27-residue peptide (27mer(I860A)) derived from phospholipase C-β3 (PLC-β3), and the small molecule BIM-46187 have also been characterized as selective G q inhibitors within the past 5 years."

Already in 2010, Professor Li Zhang and colleagues at the Xinjiang Medical University in China investigated Gq/11 expression in acute respiratory distress syndrome (ARDS) in rats. They also found that altered Gq/11 expression in lung, brain, heart, kidney, liver and small intestine might be responsible for the multi-organ injury observed (Zhang et al., 2010).

PFPC Canada


REFERENCES

Cabana J, Holleran B, Leduc R, Escher E, Guillemette G, Lavigne P - "Identification of Distinct Conformations of the Angiotensin-II Type 1 Receptor Associated with the Gq/11 Protein Pathway and the β-Arrestin Pathway Using Molecular Dynamics Simulations" J Biol Chem 290(25):15835-15854 (2015)
https://www.ncbi.nlm.nih.gov/labs/pmc/a ... MC4505491/

Canals M, Jenkins L, Kellett E, Milligan G - "Up-regulation of the angiotensin II type 1 receptor by the MAS proto-oncogene is due to constitutive activation of Gq/G11 by MAS" J Biol Chem 281(24):16757-67 (2006)
https://pubmed.ncbi.nlm.nih.gov/16611642/

Tietze D, Kaufmann D, Tietze AA, Voll A, Reher R, König G, Hausch F - "Structural and Dynamical Basis of G Protein Inhibition by YM-254890 and FR900359: An Inhibitor in Action" J Chem Inf Model 59(10):4361-4373 (2019)

Zhang H, Nielsen AL, Strømgaard K - "Recent achievements in developing selective Gq inhibitors" Med Res Rev 40(1):135-157 (2020)

Zhang L, Leifate B, Kelala A - "The dynamic alteration in Gq/11 protein expression in multiple organs during acute respiratory distress syndrome in rat" Chinese Critical Care Medicine 22(8):477-81 (2010)
https://pubmed.ncbi.nlm.nih.gov/20804650/

ALSO SEE:

Zhang L, Shi G - "Gq-Coupled Receptors in Autoimmunity" J Immunol Res 2016:3969023 (2016)
https://www.ncbi.nlm.nih.gov/pmc/articl ... 969023.pdf

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