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| Routes of administration | Infusion |
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| Elimination half-life | 2.9-11 min |
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| Formula | C150H188N57O97P15 |
| Molar mass | 4806.062 g·mol |
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BC-007, whose international nonproprietary name is Rovunaptabin, is an oligonucleotide aptamer, a synthetic DNA compound designed to bind other chemicals. BC-007 is in early-stage clinical trials as a lead compound intended for the potential treatment of heart failure or long COVID.
History
Since the 1990s, the binding of G protein coupled receptors to autoantibodies (GPCR-AABs) was investigated as a possible factor in the pathology of several diseases, including heart disease. In parallel, treatment strategies to remove GPCR-AABs were investigated, initially using proteins or peptides to bind the antibodies.
In 2012, scientists from the Max Delbrück Center and the Charité Heart Center obtained a patent in the United States for using aptamers as a therapy or diagnosis of autoimmune diseases. Beginning in 2013, the research group focused on the treatment of dilated cardiomyopathy in people positive for beta-1 adrenergic receptor autoantibodies. In 2015–16, scientists reported that two aptamers might bind and inhibit GPCR-AABs.
The biotechnology company Berlin Cures pursued the development of the aptamer with the nucleotide sequence GGT TGG TGT GGT TGG under the codename BC-007 for the inhibition of autoantibodies in cardiomyopathy.
Properties
BC-007 is a 15-nucleotide single-stranded DNA molecule consisting of nine unmodified deoxy-guanosines and six corresponding deoxythymidines with the sequence 5'-GGT TGG TGT GGT TGG-3'. Its three-dimensional structure allows it to wrap around the target structure of G-protein-coupled receptor autoantibodies and neutralize their activity.
BC-007 is synthetic, enabling it to be produced in high volumes quickly. It is stable and suited for long-term storage. It has shown no side effects in early clinical studies, and does not trigger immunological responses. As it is water soluble, it can be formulated as inhalation or as nasal spray. In some human studies, it was given by intravenous infusion, displaying an in vivo half-life in blood of about 4 minutes.
References
- "WHO Drug Information - International Nonproprietary Names for Pharmaceutical Substances (INN) - Recommended INN: List 91". INN and Classification of Medical Products (INN), World Health Organization. 2024-03-25. Archived from the original (PDF) on 2024-03-25. Retrieved 2024-04-03.
- ^ Kolter T (2023). "BC-007". In Böckler F, Dill B, Eisenbrand G, et al. (eds.). Römpp [Online]. Georg Thieme Verlag. Archived from the original on 2023-07-23.
- Matsui S, Fu ML (May 1998). "Myocardial injury due to G-protein coupled receptor-autoimmunity". Japanese Heart Journal. 39 (3): 261–274. doi:10.1536/ihj.39.261. PMID 9711178. S2CID 22133040.
- Bornholz B, Wallukat G, Roggenbuck D, Schimke I (2017-02-17). "Chapter 3 - Autoantibodies Directed Against G-Protein-Coupled Receptors in Cardiovascular Diseases: Basics and Diagnostics". In Nussinovitch U (ed.). The Heart in Rheumatic, Autoimmune and Inflammatory Diseases. Academic Press. pp. 49–63. doi:10.1016/B978-0-12-803267-1.00003-X. ISBN 978-0-12-803267-1.
- Wallukat G, Müller J, Hetzer R (November 2002). "Specific removal of beta1-adrenergic autoantibodies from patients with idiopathic dilated cardiomyopathy". The New England Journal of Medicine. 347 (22): 1806. doi:10.1056/NEJM200211283472220. PMID 12456865.
- Doesch AO, Konstandin M, Celik S, Kristen A, Frankenstein L, Hardt S, et al. (2009-07-09). "Effects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy". Journal of Clinical Apheresis. 24 (4): 141–149. doi:10.1002/jca.20204. PMID 19591221. S2CID 5566530.
- Büttner, Bettina (2012). "Technology offer - Aptamers for the Treatment and Diagnosis of Diseases Seropositive for Autoantibodies - Ref. No.: CH553" (PDF). Charité-Universitätsmedizin Berlin. Archived from the original (PDF) on 2023-04-23.
- Haberland A, Wallukat G, Schimke I (March 2013). "The patent situation concerning the treatment of diseases associated with autoantibodies directed against G-protein-coupled receptors". Pharmaceutical Patent Analyst. 2 (2): 231–248. doi:10.4155/ppa.12.88. PMID 24237028.
- Patel PA, Hernandez AF (July 2013). "Targeting anti-beta-1-adrenergic receptor antibodies for dilated cardiomyopathy". European Journal of Heart Failure. 15 (7): 724–729. doi:10.1093/eurjhf/hft065. PMC 3707431. PMID 23639780.
- Haberland A, Holtzhauer M, Schlichtiger A, Bartel S, Schimke I, Müller J, et al. (October 2016). "Aptamer BC 007 - A broad spectrum neutralizer of pathogenic autoantibodies against G-protein-coupled receptors". European Journal of Pharmacology. 789: 37–45. doi:10.1016/j.ejphar.2016.06.061. PMID 27375076.
- Wallukat G, Müller J, Haberland A, Berg S, Schulz A, Freyse EJ, et al. (January 2016). "Aptamer BC007 for neutralization of pathogenic autoantibodies directed against G-protein coupled receptors: A vision of future treatment of patients with cardiomyopathies and positivity for those autoantibodies". Atherosclerosis. 244: 44–47. doi:10.1016/j.atherosclerosis.2015.11.001. PMID 26584137.
- "Berlin Cures Announces Successful Completion of Phase 1 Study of BC 007 for the Treatment of Cardiomyopathy". BioSpace. 2018-08-22. Archived from the original on 2023-05-30. Retrieved 2023-05-30.
- ^ Lang, Carolin (2020-07-08). "Wirkstoff-Kandidat auf DNA Basis - Mit James Bond gegen Covid-19" [Drug candidate based on DNA - Fighting Covid-19 with James Bond]. Pharmazeutische Zeitung (PZ) - Die Zeitschrift der deutschen Apotheker (in German). Avoxa - Mediengruppe Deutscher Apotheker GmbH. ISSN 0031-7136. Archived from the original on 2020-07-08. Retrieved 2024-04-09.