Update on MicroRNA-based Treatment Strategies

2021 ◽  
Vol 30 (03) ◽  
pp. 243-250
Author(s):  
Eric Hesse ◽  
Franz Jakob ◽  
Hanna Taipaleenmäki
Keyword(s):  
Treatment Strategies ◽  
Protein Coding ◽  
Therapeutic Implications ◽  
The Public ◽  
Drug Candidates ◽  
Diagnostic Use ◽  
Recent Success ◽  
Novel Approach ◽  
Novel Drugs ◽  
Novel Drug

AbstractThe family of RNAs comprises several members, protein coding mRNAs and a larger group of non-coding RNAs, which include small, approximately 21-25 nucleotides long microRNAs (miRNAs). In addition to an evolving diagnostic use of RNAs, RNA-based drugs are emerging very rapidly in medicine, which is not only -but currently very prominently visible- due to the impressive success of the first-in-class Covid-19 vaccines such as Comirnaty and Moderna (marketed by the companies Biontech/Pfizer and Moderna, respectively). Although administration of RNA-based drugs comes along with several technical obstacles including delivery approaches, the technology is experiencing a breakthrough and technical and conceptual hurdles that may still remain are very likely to be overcome within the near future. It is therefore highly likely that RNA-based pharmacotherapies may revolutionize medicine by improving vaccination concepts but also by providing novel drugs to treat many other conditions like cancer, metabolic- and degenerative diseases and beyond. It is fascinating to witness the rise of such milestones in medicine and is tempting to elaborate which additional accomplishments can be made using this technology towards personalized medicine comprising diagnostic and therapeutic aspects as well as individual drug design.Although the most recent success with mRNA-based and therefore protein coding vaccines currently takes center stage in media and people’s life, other types of RNAs that are less prominent to the public, like non-coding miRNAs, also develop very successfully towards diagnostic and therapeutic purposes. While the diagnostic use of miRNAs was reviewed in another article in this issue (see article from Hackl et al., this issue), this brief review will provide an update on the emerging therapeutic implications of miRNAs. Despite the fact that no miRNA-based drug has yet reached clinical approval, several compounds are in pre-clinical and clinical development for the treatment of various diseases and great progress has been made during the recent years, which also facilitated the establishment of several innovative biotech companies.Several obstacles associated with this novel approach including off-target effects, tissue specificity and delivery systems exist. However, important improvements have already been made and will continue to be made. It can therefore be assumed that treatments using this class of RNA will also further progress and stimulate additional stakeholders to enter the field to develop novel drug candidates as first-in-class medicinal products to address highly unmet clinical needs. This technology is still at its infancy given that miRNAs were uncovered just about 20 years ago but the conditions are promising for the development of next generation miRNA-based drugs.

scholarly journals Missing Novelty in Drug Development

2021 ◽  
Author(s):  
Joshua Krieger ◽  
Danielle Li ◽  
Dimitris Papanikolaou
Keyword(s):  
Radical Innovation ◽  
Chemical Similarity ◽  
Net Worth ◽  
Drug Candidates ◽  
Pharmaceutical Firms ◽  
External Finance ◽  
Fda Approval ◽  
Novel Drugs ◽  
Positive Shock ◽  
Novel Drug

Abstract We provide evidence that risk aversion leads pharmaceutical firms to underinvest in radical innovation. We introduce a new measure of drug novelty based on chemical similarity and show that firms face a risk-reward trade-off: novel drug candidates are less likely to obtain FDA approval but are based on more valuable patents. Consistent with a simple model of costly external finance, we show that a positive shock to firms’ net worth leads firms to develop more novel drugs. This suggests that even large firms may behave as though they are risk averse, reducing their willingness to investment in potentially valuable radical innovation.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

Oncology ◽  
2017 ◽  
pp. 434-481
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

scholarly journals Deep Learning in Drug Discovery and Medicine; Scratching the Surface

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2384 ◽  
Author(s):  
Dibyendu Dana ◽  
Satishkumar Gadhiya ◽  
Luce St. Surin ◽  
David Li ◽  
Farha Naaz ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Precision Medicine ◽  
A Priori ◽  
Treatment Strategies ◽  
Molecular Therapy ◽  
Molecular Profile ◽  
Drug Candidates ◽  
Practice Of Medicine ◽  
New Chemical Entities ◽  
Novel Drug

The practice of medicine is ever evolving. Diagnosing disease, which is often the first step in a cure, has seen a sea change from the discerning hands of the neighborhood physician to the use of sophisticated machines to use of information gleaned from biomarkers obtained by the most minimally invasive of means. The last 100 or so years have borne witness to the enormous success story of allopathy, a practice that found favor over earlier practices of medical purgatory and homeopathy. Nevertheless, failures of this approach coupled with the omics and bioinformatics revolution spurred precision medicine, a platform wherein the molecular profile of an individual patient drives the selection of therapy. Indeed, precision medicine-based therapies that first found their place in oncology are rapidly finding uses in autoimmune, renal and other diseases. More recently a new renaissance that is shaping everyday life is making its way into healthcare. Drug discovery and medicine that started with Ayurveda in India are now benefiting from an altogether different artificial intelligence (AI)—one which is automating the invention of new chemical entities and the mining of large databases in health-privacy-protected vaults. Indeed, disciplines as diverse as language, neurophysiology, chemistry, toxicology, biostatistics, medicine and computing have come together to harness algorithms based on transfer learning and recurrent neural networks to design novel drug candidates, a priori inform on their safety, metabolism and clearance, and engineer their delivery but only on demand, all the while cataloging and comparing omics signatures across traditionally classified diseases to enable basket treatment strategies. This review highlights inroads made and being made in directed-drug design and molecular therapy.

Integrated in Silico Methods for the Design and Optimization of Novel Drug Candidates

2015 ◽  
pp. 269-317
Author(s):  
Nikola Minovski ◽  
Marjana Novič
Keyword(s):  
In Silico ◽  
Comprehensive Overview ◽  
Design And Optimization ◽  
Drug Candidates ◽  
In Silico Drug Design ◽  
Current Trends ◽  
Novel Drugs ◽  
Screening Protocol ◽  
Cost Efficient ◽  
Novel Drug

Although almost fully automated, the discovery of novel, effective, and safe drugs is still a long-term and highly expensive process. Consequently, the need for fleet, rational, and cost-efficient development of novel drugs is crucial, and nowadays the advanced in silico drug design methodologies seem to effectively meet these issues. The aim of this chapter is to provide a comprehensive overview of some of the current trends and advances in the in silico design of novel drug candidates with a special emphasis on 6-fluoroquinolone (6-FQ) antibacterials as potential novel Mycobacterium tuberculosis DNA gyrase inhibitors. In particular, the chapter covers some of the recent aspects of a wide range of in silico drug discovery approaches including multidimensional machine-learning methods, ligand-based and structure-based methodologies, as well as their proficient combination and integration into an intelligent virtual screening protocol for design and optimization of novel 6-FQ analogs.

scholarly journals Current and promising novel drug candidates against visceral leishmaniasis

2019 ◽  
Vol 91 (8) ◽  
pp. 1385-1404 ◽  
Author(s):  
Rosa M. Reguera ◽  
Yolanda Pérez-Pertejo ◽  
Camino Gutiérrez-Corbo ◽  
Bárbara Domínguez-Asenjo ◽  
César Ordóñez ◽  
...  
Keyword(s):  
Low Income ◽  
Neglected Tropical Diseases ◽  
Zoonotic Diseases ◽  
Low Income Countries ◽  
Drug Candidates ◽  
Novel Drugs ◽  
Early Case ◽  
New Treatments ◽  
Novel Drug ◽  
Early Case Detection

Abstract Leishmaniasis is a group of zoonotic diseases caused by a trypanosomatid parasite mostly in impoverished populations of low-income countries. In their different forms, leishmaniasis is prevalent in more than 98 countries all over the world and approximately 360-million people are at risk. Since no vaccine is currently available to prevent any form of the disease, the control strategy of leishmaniasis mainly relies on early case detection followed by adequate pharmacological treatment that may improve the prognosis and can reduce transmission. A handful of compounds and formulations are available for the treatment of leishmaniasis in humans, but only few of them are currently in use since most of these agents are associated with toxicity problems such as nephrotoxicity and cardiotoxicity in addition to resistance problems. In recent decades, very few novel drugs, new formulations of standard drugs or combinations of them have been approved against leishmaniasis. This review highlights the current drugs and combinations that are used medical practice and recent advances in new treatments against leishmaniasis that were pointed out in the recent 2nd Conference, Global Challenges in Neglected Tropical Diseases, held in San Juan, Puerto Rico in June 2018, emphasizing the plethora of new families of molecules that are bridging the gap between preclinical and first-in-man trials in next future.

scholarly journals Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on In Vitro and In Vivo Studies

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2911 ◽  
Author(s):  
Ashok Aspatwar ◽  
Jean-Yves Winum ◽  
Fabrizio Carta ◽  
Claudiu Supuran ◽  
Milka Hammaren ◽  
...  
Keyword(s):  
Drug Targets ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Carbonic Anhydrases ◽  
Novel Approach ◽  
Novel Drugs ◽  
Novel Treatment Strategies ◽  
Inhibition Studies

Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, β-carbonic anhydrases (β-CAs) have emerged as potential drug targets in mycobacteria. The genomes of mycobacteria encode for three β-CAs that have been cloned and characterized from Mycobacterium tuberculosis (Mtb) and the crystal structures of two of the enzymes have been determined. Different classes of inhibitor molecules against Mtb β-CAs have subsequently been designed and have been shown to inhibit these mycobacterial enzymes in vitro. The inhibition of these centrally important mycobacterial enzymes leads to reduced growth of mycobacteria, lower virulence, and impaired biofilm formation. Thus, the inhibition of β-CAs could be a novel approach for developing drugs against the severe diseases caused by pathogenic mycobacteria. In the present article, we review the data related to in vitro and in vivo inhibition studies in the field.

Mucoadhesive microspheres: An Emerging trends in therapy of diabetes mellitus.

2020 ◽  
Vol 16 ◽  
Author(s):  
Deepika Singh ◽  
Deepak Choudhary
Keyword(s):  
Diabetes Mellitus ◽  
Treatment Strategies ◽  
Antidiabetic Drugs ◽  
The Novel ◽  
Major Health ◽  
Advantages And Disadvantages ◽  
Emerging Trends ◽  
Novel Approach ◽  
Narrative Literature ◽  
Novel Drug

Introduction: Diabetes mellitus is concluded as a one of major health problems which is associated with the excessive glucose level in blood. Various conventional therapies are marketed available which have adverse effects and not effected too much. Materials and Method: After focusing on the disadvantages of the conventional drugs the novel drug delivery system (NDDS) came into existence and make revolutionary changes in the field of pharmaceutical industry. This paper focused on the types of diabetes mellitus, NDDS and treatment strategies for the diabetes mellitus. Result: Mucoadhesive microspheres are an interesting and emerging field for encapsulated the conventional molecule. This paper provides the detail information on the advantages and disadvantages of microsphere. Narrative literature by authors using the antidiabetic drugs to formulated into micropsheres. Conclusion: In short, mucoadhsevie microspheres are a novel approach to overcome the disavadantages associated with the antidiabetic drugs.

scholarly journals Therapeutic implications of microRNAs in human cancer

2011 ◽  
Vol 2 (1) ◽  
pp. 3
Author(s):  
Michael Rossbach
Keyword(s):  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Tumor Development ◽  
Gene Profiling ◽  
Protein Coding ◽  
Expression Levels ◽  
Therapeutic Implications ◽  
Novel Drugs ◽  
Antisense Constructs

MicroRNAs (miRNAs) are a class of highly evolutionarily conserved non-coding RNAs (ncRNAs) that modulate gene expression. Several studies have shown that the expression of miRNAs is deregulated in human malignancies. For ncRNAs and miRNAs, such gene-profiling studies in tumorigenic tissues have identified significant signatures that are of both diagnostic and prognostic value. Addressing the functions of ncRNAs not only give insights into the molecular mechanisms that underlie complex genetic processes, but may also elucidate novel mechanisms that contribute to early stages of tumor development, progression and metastasis. MiRNA-based novel approaches target the ncRNAome, including, for instance, miRNA expression levels and improved designs of miRNA-mimics or more precise target-predictions, prevent off-target effects of novel drugs and make miRNAs become a highly efficient class of therapeutics. For miRNA-based therapeutic studies two direct strategies are currently under investigation, viz. (i) the overexpression of given miRNAs to inhibit the expression of protein-coding genes or (ii) the inhibition of target miRNAs with antisense constructs like antagomiRs. Indirect strategies include the use of novel drugs that modulate miRNA expression levels by directly targeting their processing or transcription. Further, miRNA-based biomarkers have a significant impact on the development of both therapeutic and diagnostic agents, a concept known as theranostics and are highly relevant for drug development and personalized medicine.

Current Status in the Design and Development of Agonists and Antagonists of Adenosine A3 Receptor as Potential Therapeutic Agents

2019 ◽  
Vol 25 (25) ◽  
pp. 2772-2787 ◽  
Author(s):  
Raghu P. Mailavaram ◽  
Omar H.A. Al-Attraqchi ◽  
Supratik Kar ◽  
Shinjita Ghosh
Keyword(s):  
Drug Target ◽  
Therapeutic Agents ◽  
G Protein Coupled Receptors ◽  
Current Status ◽  
Renal Diseases ◽  
Adenosine A3 Receptor ◽  
Drug Candidates ◽  
Novel Drugs ◽  
The Family ◽  
G Protein Coupled

Adenosine receptors (ARs) belongs to the family of G-protein coupled receptors (GPCR) that are responsible for the modulation of a wide variety of physiological functions. The ARs are also implicated in many diseases such as cancer, arthritis, cardiovascular and renal diseases. The adenosine A3 receptor (A3AR) has emerged as a potential drug target for the progress of new and effective therapeutic agents for the treatment of various pathological conditions. This receptor’s involvement in many diseases and its validity as a target has been established by many studies. Both agonists and antagonists of A3AR have been extensively investigated in the last decade with the goal of developing novel drugs for treating diseases related to immune disorders, inflammation, cancer, and others. In this review, we shall focus on the medicinal chemistry of A3AR ligands, exploring the diverse chemical classes that have been projected as future leading drug candidates. Also, the recent advances in the therapeuetic applications of A3AR ligands are highlighted.

The Impact of Translational Research in Breast Cancer Care: Can we Improve the Therapeutic Scenario?

2018 ◽  
Vol 18 (6) ◽  
pp. 832-836
Author(s):  
Giuseppe Buono ◽  
Francesco Schettini ◽  
Francesco Perri ◽  
Grazia Arpino ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Translational Research ◽  
Cell Biology ◽  
Cancer Biology ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Molecular Heterogeneity ◽  
Therapeutic Implications ◽  
The Impact

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

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