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Cholesterol Lowering Biotechnological Strategies: From Monoclonal Antibodies to Antisense Therapies. A Pre-Clinical Perspective Review

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Abstract

In recent years, the increase in available genetic information and a better understanding of the genetic bases of dyslipidemias has led to the identification of potential new avenues for therapies. Additionally, the development of new technologies has presented the key for developing novel therapeutic strategies targeting not only proteins (e.g., the monoclonal antibodies and vaccines) but also the transcripts (from antisense oligonucleotides (ASOs) to small interfering RNAs) or the genomic sequence (gene therapies). These pharmacological advances have led to successful therapeutic improvements, particularly in the cardiovascular arena because we are now able to treat rare, genetically driven, and previously untreatable conditions (e.g, familial hypertriglyceridemia or hyperchylomicronemia). In this review, the pre-clinical pharmacological development of the major biotechnological cholesterol lowering advances were discussed, describing facts, gaps, potential future steps forward, and therapeutic opportunities.

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Acknowledgements

The authors’ research is supported by: EXTRALIPO “New lipid-oriented pharmacological and chemical approaches to discriminate and unravel extracellular vesicles biological functions” Bando SEED – PSR 2019 (SB); Russian Ministry of Science and Higher Education (Agreement No. 075-15-2020-901) (ASA); H2020 REPROGRAM PHC-03-2015/667837-2 (ALC); Fondazione Cariplo 2015-0524 and 2015-0564 (ALC); ERANET ER-2017-2364981 (ALC); Ministry of Health-IRCCS MultiMedica GR-2011-02346974 (ALC); PRIN 2017H5F943 (ALC); “Cibo, Microbiota, Salute” by “Vini di Batasiolo S.p.A” AL_RIC19ABARA_01 (AB), “Post-Doctoral Fellowship 2020” by “Fondazione Umberto Veronesi” 2020-3318 (AB); a research grant 2021 from “the Peanut Institute”.

Funding

This work has been supported by the Italian Ministry of Health - Ricerca Corrente - IRCCS MultiMedica.

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Authors and Affiliations

  1. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy

    S. Bellosta, C. Rossi, A. S. Alieva, A. L. Catapano, A. Corsini & A. Baragetti

  2. Almazov National Medical Research Centre, Saint Petersburg, Russia

    A. S. Alieva

  3. IRCCS MultiMedica, via Fantoli 16, 20138, Milan, Italy

    A. L. Catapano, A. Corsini & A. Baragetti

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  1. S. Bellosta
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  2. C. Rossi
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  3. A. S. Alieva
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  4. A. L. Catapano
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  5. A. Corsini
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  6. A. Baragetti
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Contributions

Conceptualization, literature search, writing original draft: S. Bellosta, A. Baragetti; Review and editing: C. Rossi, A.S. Alieva, A. Corsini; Supervision: A.L. Catapano. All authors have read and approved the final manuscript.

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Correspondence to A. Corsini.

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Publication of the article is approved by all authors and tacitly by the responsible authorities of the University of Milan and Multimedica, where the work was carried out.

Competing Interests

A.L. Catapano has received honoraria, lecture fees, or research grants from Sigma-Tau, Menarini, Kowa, Recordati, Eli Lilly, Astrazeneca, Mediolanum, Pfizer, Merck, Sanofi, Aegerion, Amgen, Genzyme, Bayer, Sanofi, and Regeneron Daiichi-Sankyo.

A. Corsini has received honoraria from Amgen, Astra Zeneca, Daiichi Sankyo, Sanofi, Novartis, DOC, TEVA and Servier, and grants from Daiichi Sankyo and PIAM.

S. Bellosta, C. Rossi, A.S. Alieva, and A. Baragetti have no relevant financial or non-financial interests to disclose.

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Bellosta, S., Rossi, C., Alieva, A.S. et al. Cholesterol Lowering Biotechnological Strategies: From Monoclonal Antibodies to Antisense Therapies. A Pre-Clinical Perspective Review. Cardiovasc Drugs Ther 37, 585–598 (2023). https://doi.org/10.1007/s10557-021-07293-w

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