scholarly journals RNA Therapeutics - Research and Clinical Advancements

2021 ◽  
Vol 8 ◽  
Author(s):  
Rundong Feng ◽  
Suryaji Patil ◽  
Xin Zhao ◽  
Zhiping Miao ◽  
Airong Qian
Keyword(s):  
Drug Administration ◽  
Antisense Oligonucleotides ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Delivery Systems ◽  
Rna Modification ◽  
Small Interfering Rnas ◽  
Suitable Treatment ◽  
Non Coding Rnas ◽  
Targeting Ability

RNA therapeutics involve the use of coding RNA such as mRNA as well as non-coding RNAs such as small interfering RNAs (siRNA), antisense oligonucleotides (ASO) to target mRNA, aptamers, ribozymes, and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR/Cas) endonuclease to target proteins and DNA. Due to their diverse targeting ability and research in RNA modification and delivery systems, RNA-based formulations have emerged as suitable treatment options for many diseases. Therefore, in this article, we have summarized different RNA therapeutics, their targeting strategies, and clinical progress for various diseases as well as limitations; so that it might help researchers formulate new and advanced RNA therapeutics for various diseases. Additionally, U.S. Food and Drug Administration (USFDA)-approved RNA-based therapeutics have also been discussed.

scholarly journals A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020

2021 ◽  
Author(s):  
Gizem Kayki-Mutlu ◽  
Martin C. Michel
Keyword(s):  
Small Molecules ◽  
Drug Administration ◽  
Antisense Oligonucleotides ◽  
Food And Drug Administration ◽  
New Drugs ◽  
Small Interfering Rnas ◽  
Drug Discovery And Development ◽  
The Past ◽  
The Us ◽  
Approved Drugs

AbstractWhile the COVID-19 pandemic also affected the work of regulatory authorities, the US Food and Drug Administration approved a total of 53 new drugs in 2020, one of the highest numbers in the past decades. Most newly approved drugs related to oncology (34%) and neurology (15%). We discuss these new drugs by level of innovation they provide, i.e., first to treat a condition, first using a novel mechanisms of action, and “others.” Six drugs were first in indication, 15 first using a novel mechanism of action, and 32 other. This includes many drugs for the treatment of orphan indications and some for the treatment of tropical diseases previously neglected for commercial reasons. Small molecules continue to dominate new drug approvals, followed by antibodies. Of note, newly approved drugs also included small-interfering RNAs and antisense oligonucleotides. These data show that the trend for declines in drug discovery and development has clearly been broken.

Ginkgo biloba and vitamin E for Alzheimer's disease

2012 ◽  
Vol 1 (11) ◽  
pp. 283-284
Author(s):  
Chris Paxos
Keyword(s):  
United States ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Drug Administration ◽  
Ginkgo Biloba ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
The United States ◽  
Additional Treatment

Alzheimer's disease affects an estimated 35 million people worldwide, with over 5 million affected in the United States. Few medications are currently approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease; subsequently, patients and caregivers often look for additional treatment options. This article reviews studies evaluating the use of Ginkgo biloba and vitamin E for the treatment of Alzheimer's disease.

scholarly journals The African Green Monkey Model of Pneumonic Plague and US Food and Drug Administration Approval of Antimicrobials Under the Animal Rule

2020 ◽  
Vol 70 (Supplement_1) ◽  
pp. S51-S59
Author(s):  
Judith A Hewitt ◽  
Lynda L Lanning ◽  
Joseph L Campbell
Keyword(s):  
Drug Administration ◽  
Human Disease ◽  
Case Reports ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Lethal Dose ◽  
Additional Treatment ◽  
Primary Data ◽  
Pneumonic Plague ◽  
Multiple Drugs

Abstract Background Additional treatment options for pneumonic plague, the most severe form of infection by Yersinia pestis, are needed, as past US Food and Drug Administration (FDA) approvals were not based on clinical trials that meet today’s standards, and multiple drugs are sought to counter resistance or use in special populations. Due to the sporadic nature of outbreaks and the low number of pneumonic cases of disease, we sought FDA approval of antimicrobials for treatment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 or more well-characterized animal models that sufficiently represent human disease. Methods A model was developed in African green monkeys (AGMs) after challenge with a lethal dose of Y. pestis delivered as an aerosol, in 4 independent studies in 3 laboratories. The primary data points were bacteremia (daily), body temperature and heart rate (continuously monitored by telemetry), and survival. In antimicrobial efficacy studies, human-equivalent doses of gentamicin, ciprofloxacin, levofloxacin, and doxycycline were administered upon fever onset for 10 days. Results Disease in AGMs was similar to case reports of human disease. Fever was determined to be a reliable sign of disease and selected as a treatment trigger. Gentamicin was 60%–80% effective depending on the dose given to animals. Ciprofloxacin and levofloxacin were found to be >90% efficacious. These data were submitted to FDA and plague indications were approved. Doxycycline was less effective. Conclusions The AGM model of pneumonic plague is reproducible, well-characterized, and mimics human disease. It has been used to support plague indications for fluoroquinolones and to test the efficacy of additional antimicrobials.

Therapeutic targeting of non-coding RNAs

2013 ◽  
Vol 54 ◽  
pp. 127-145 ◽  
Author(s):  
Thomas C. Roberts ◽  
Matthew J.A. Wood
Keyword(s):  
Gene Expression ◽  
Antisense Oligonucleotides ◽  
Regulation Of Gene Expression ◽  
Gene Activation ◽  
Mature Mirnas ◽  
Transcriptional Gene Silencing ◽  
Small Interfering Rnas ◽  
Promising Therapeutic Approach ◽  
Non Coding Rnas ◽  
Mirna Sponges

ncRNAs (non-coding RNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. In the present chapter we consider two classes of ncRNA: miRNAs (microRNAs) which are post-transcriptional regulators of gene expression and lncRNAs (long ncRNAs) which mediate interactions between epigenetic remodelling complexes and chromatin. Mutation and misexpression of ncRNAs have been implicated in many disease conditions and, as such, pharmacological modulation of ncRNAs is a promising therapeutic approach. miRNA activity can be antagonized with antisense oligonucleotides which sequester or degrade mature miRNAs, and expressed miRNA sponges which compete with target transcripts for miRNA binding. Conversely, synthetic or expressed miRNA mimics can be used to treat a deficiency in miRNA expression. Similarly, conventional antisense technologies can be used to silence lncRNAs. Targeting promoter-associated RNAs with siRNAs (small interfering RNAs) results in recruitment of chromatin-modifying activities and induces transcriptional gene silencing. Alternatively, targeting natural antisense transcripts with siRNAs or antisense oligonucleotides can abrogate endogenous epigenetic silencing leading to transcriptional gene activation. The ability to modulate gene expression at the epigenetic level presents exciting new opportunities for the treatment of human disease.

scholarly journals An Update on Eight “New” Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

2021 ◽  
Vol 10 (5) ◽  
pp. 1068
Author(s):  
Erlangga Yusuf ◽  
Hannelore I. Bax ◽  
Nelianne J. Verkaik ◽  
Mireille van Westreenen
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Beta Lactamases ◽  
New Antibiotics ◽  
Tract Infections ◽  
The U.S

Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).

scholarly journals The Interdisciplinary Stem Cell Institute’s Use of Food and Drug Administration-Expanded Access Guidelines to Provide Experimental Cell Therapy to Patients With Rare Serious Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Aisha Khan ◽  
Michael A. Bellio ◽  
Ivonne H. Schulman ◽  
Allan D. Levi ◽  
Bangon Longsomboon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Complex Congenital Heart Disease ◽  
Allogeneic Bone ◽  
Expanded Access ◽  
Cell Based Therapy ◽  
Cord Injury ◽  
Brain Stem Injury

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

US Food and Drug Administration (FDA): Benefit-Risk Considerations for Cefiderocol (Fetroja®)

2020 ◽  
Author(s):  
Shabnam Naseer ◽  
Edward A Weinstein ◽  
Daniel B Rubin ◽  
Kalavati Suvarna ◽  
Xiaohui Wei ◽  
...  
Keyword(s):  
Drug Administration ◽  
Nosocomial Pneumonia ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Bloodstream Infections ◽  
Gram Negative Bacteria ◽  
Open Label ◽  
Double Blind ◽  
Gram Negative ◽  
Tract Infections

Abstract In November 2019, the Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible gram-negative bacteria in adults with limited to no alternative treatment options based on a randomized, double-blind, noninferiority cUTI trial (APEKS-cUTI). In a randomized, open-label trial (CREDIBLE-CR) in patients with cUTI, nosocomial pneumonia, bloodstream infections, or sepsis due to carbapenem-resistant gram-negative bacteria, an increase in all-cause mortality was observed in patients treated with cefiderocol as compared to best available therapy. The cause of the increased mortality was not established, but some deaths were attributed to treatment failure. Preliminary data from a randomized, double-blind trial (APEKS-NP) in patients with nosocomial pneumonia due to carbapenem-susceptible gram-negative bacteria showed a similar rate of mortality as compared to meropenem. We describe the uncertainties and challenges in the interpretation of the CREDIBLE-CR trial and some benefit-risk considerations for the use of cefiderocol in clinical practice. Clinical Trials Registration NCT02714595.

scholarly journals Treatment in AML and MDS Patients Who Are Ineligible for Intensive Chemotherapy: Using Social Media Intelligence to Capture What Really Matters to Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4826-4826
Author(s):  
Alison Booth ◽  
Timothy J Bell ◽  
Sonia Halhol ◽  
Shiyu Pan ◽  
Verna L Welch ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Social Media ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Treatment Options ◽  
Treatment Decisions ◽  
Intensive Chemotherapy ◽  
Employment Equity ◽  
Equity Ownership

Abstract Objectives: Treatment options for patients with AML/MDS who are ineligible for intensive chemotherapy are limited. Due to rapid progression of the condition it is difficult to capture what is most important to patients when making treatment decisions. Social media data is a rich source of information, and the FDA recently encouraged stakeholders to explore the use of social media to capture the patient perspective.[i] This study aimed to capture factors most important to patients ineligible for intensive chemotherapy through using disease-specific social media posts by patients and/or their caregivers. Identifying these factors will give clinicians a better understanding of what is important to their patients when considering their treatment. Methods: AML and MDS patient/caregiver posts were extracted from publicly available discussions on three large AML/MDS-specific sites. Posts were manually reviewed to only include the experience of patients ineligible for intensive chemotherapy. 1,443 posts from 220 AML patients/caregivers and 2,733 posts from 127 MDS patients/caregivers were included. A targeted search for terms relating to end of life treatment decisions was conducted within the included posts, yielding 83 posts from 40 AML users and 70 posts from 39 MDS users. These posts were manually reviewed, and relevant text segments (discussing why patients wish to live longer and reasons/motives for treatment decisions) were highlighted using a qualitative analysis approach. Results: Of the reviewed data, 40 posts from 27 AML users and 20 posts from 18 MDS users contained relevant information. A theme important to patients and caregivers was spending time with family and making memories (in 20% of relevant posts). Often reported was the desire to reach family occasions including birthdays, Christmas, anniversaries, and weddings. Quality of life was also an important consideration (in 33% of relevant posts). Many patients expressed a wish to have better quality of life over quantity of life, and did not want the risk of suffering from side effects. Tied into this was the clear preference to be at home rather than in a hospital or care home (in over 22% of relevant posts). To some patients, it was important to try all possible treatment options, and some reported their doctors were supportive of this. However a lack of available treatments was also perceived by some patients as if their doctors give up on treating them too soon. Discussion: Treatment decisions in patients with AML/MDS are complex and unique to each patient. From this analysis, it is clear being home and spending time with family was associated with a perceived higher level of quality of life for patients and caregivers. Patients and caregivers place high importance on treatment options that provide better perceived QoL over treatments that provide a moderate extension to life expectancy and require hospitalisation. This study highlights the need to consider patient perceptions of QoL and the importance of understanding patient and caregiver goals and opinions to best determine personalised treatment options. [i] United States Food and Drug Administration (FDA). June 2018. Patient-Focused Drug Development: Collecting Comprehensive and Representative Input Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders. Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM610442.pdf [accessed July 24, 2018]. Disclosures Booth: Evidera: Employment. Bell:Pfizer: Employment, Equity Ownership. Halhol:Evidera: Employment. Pan:Evidera: Employment. Welch:Pfizer: Employment, Equity Ownership. Merinopoulou:Evidera: Employment. Lambrelli:Evidera: Employment. Cox:Evidera: Employment.

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