scholarly journals Repurposing Drugs to Treat Heart and Brain Illness

2021 ◽  
Vol 14 (6) ◽  
pp. 573
Author(s):  
Maranda S. Cantrell ◽  
Alejandro Soto-Avellaneda ◽  
Jackson D. Wall ◽  
Aaron D. Ajeti ◽  
Brad E. Morrison ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Neurodegenerative Diseases ◽  
Disease Progression ◽  
Drug Repurposing ◽  
Pharmacological Treatments ◽  
Representative Case ◽  
Inflammatory Processes ◽  
Expensive Process ◽  
Selection Of

Drug development is a complicated, slow and expensive process with high failure rates. One strategy to mitigate these factors is to recycle existing drugs with viable safety profiles and have gained Food and Drug Administration approval following extensive clinical trials. Cardiovascular and neurodegenerative diseases are difficult to treat, and there exist few effective therapeutics, necessitating the development of new, more efficacious drugs. Recent scientific studies have led to a mechanistic understanding of heart and brain disease progression, which has led researchers to assess myriad drugs for their potential as pharmacological treatments for these ailments. The focus of this review is to survey strategies for the selection of drug repurposing candidates and provide representative case studies where drug repurposing strategies were used to discover therapeutics for cardiovascular and neurodegenerative diseases, with a focus on anti-inflammatory processes where new drug alternatives are needed.

scholarly journals Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 14 (3) ◽  
pp. 280
Author(s):  
Rita Rebelo ◽  
Bárbara Polónia ◽  
Lúcio Lara Santos ◽  
M. Helena Vasconcelos ◽  
Cristina P. R. Xavier
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Pancreatic Ductal Adenocarcinoma ◽  
De Novo ◽  
Drug Repurposing ◽  
Metastatic Tumor ◽  
Therapeutic Options ◽  
Ductal Adenocarcinoma ◽  
Clinical Indication ◽  
Novel Treatments

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is time-efficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.

scholarly journals Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases

2020 ◽  
Vol 18 ◽  
Author(s):  
Graziella dos Reis Franco ◽  
Scott Smid ◽  
Cláudio Viegas
Keyword(s):  
Drug Development ◽  
Neurodegenerative Diseases ◽  
Disease Progression ◽  
Potential Application ◽  
Neurological Diseases ◽  
Drug Candidates ◽  
Disease Modifying ◽  
Pharmacological Potential ◽  
General Aspects ◽  
State Of Art

: In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer's (AD), Parkinson's (PD) and Huntington's disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present a state of art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.

scholarly journals The Challenges of Designing and Implementing Clinical Trials With Broccoli Sprouts… and Turning Evidence Into Public Health Action

2021 ◽  
Vol 8 ◽  
Author(s):  
Jed W. Fahey ◽  
Thomas W. Kensler
Keyword(s):  
Public Health ◽  
Clinical Trials ◽  
Clinical Studies ◽  
Randomized Clinical Trials ◽  
Public Health Action ◽  
Broccoli Sprouts ◽  
Health Action ◽  
Inflammatory Processes ◽  
Broccoli Sprout ◽  
Selection Of

Broccoli sprouts are a convenient and rich source of the glucosinolate glucoraphanin, which can generate the chemopreventive agent sulforaphane through the catalytic actions of plant myrosinase or β-thioglucosidases in the gut microflora. Sulforaphane, in turn, is an inducer of cytoprotective enzymes through activation of Nrf2 signaling, and a potent inhibitor of carcinogenesis in multiple murine models. Sulforaphane is also protective in models of diabetes, neurodegenerative disease, and other inflammatory processes, likely reflecting additional actions of Nrf2 and interactions with other signaling pathways. Translating this efficacy into the design and implementation of clinical chemoprevention trials, especially food-based trials, faces numerous challenges including the selection of the source, placebo, and dose as well as standardization of the formulation of the intervention material. Unlike in animals, purified sulforaphane has had very limited use in clinical studies. We have conducted a series of clinical studies and randomized clinical trials to evaluate the effects of composition (glucoraphanin-rich [± myrosinase] vs. sulforaphane-rich or mixture beverages), formulation (beverage vs. tablet) and dose, on the efficacy of these broccoli sprout-based preparations to evaluate safety, pharmacokinetics, pharmacodynamic action, and clinical benefit. While the challenges for the evaluation of broccoli sprouts in clinical trials are themselves formidable, further hurdles must be overcome to bring this science to public health action.

Developing Novel Anticancer Drugs for Targeted Populations: An Update

2020 ◽  
Vol 26 ◽  
Author(s):  
Tadesse Bekele Tafesse ◽  
Mohammed Hussen Bule ◽  
Fazlullah Khan ◽  
Mohammad Abdollahi ◽  
Mohsen Amini
Keyword(s):  
Drug Discovery ◽  
Drug Development ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Development Process ◽  
De Novo ◽  
Drug Repurposing ◽  
Drug Discovery And Development ◽  
Probability Of Success ◽  
Selection Of

Background: Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process; the rate of opportunity to get new, safe and efficacious drugs for the targeted population including pediatric patients with cancer becomes sluggish. Objectives: This paper discusses the development of novel anticancer drugs focusing on the identification and selection of target anticancer drug development for the targeted population. Methods: Information presented in this review was obtained from different databases including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. Results: The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which takes 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10-17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. Conclusion: Therefore, to continue with the progress of developing novel anticancer drugs towards the targeted population, identification and selection of the target to the specific disease type is important considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we consider the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.

scholarly journals The search for surrogacy in patient derived xenograft mouse trials: glass is less than half full

2020 ◽  
Author(s):  
Hitesh B. Mistry
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Disease Progression ◽  
Treatment Effect ◽  
Patient Survival ◽  
Surrogate Marker ◽  
Tumour Burden ◽  
Patient Derived Xenograft ◽  
Clinical Community ◽  
Large Patient

AbstractDespite the efforts of many within the drug development and clinical community surrogate biomarkers for patient survival have remained elusive in Oncology. This failure in part is attributable to there being a paucity of clinical trials showing a treatment effect on patient survival. Given this issue an alternative system to explore the surrogacy potential of biomarkers are large preclinical xenograft studies i.e. panel of patient derived xenografts or mouse clinical trials. In this study we explored the surrogacy potential of tumour burden biomarkers, current size of tumour and how its changed, preclinically in a large patient derived xenograft database which contains a diverse number of drugs/treatments (n=61) and xenografts (n=245). We found that of the possible 1830 two-arm mouse trials, 1103 showed a treatment effect on the preclinical end-point, disease progression, (p<0.05). Of these only in 30% did tumour burden markers fully capture the treatment effect on disease progression times i.e. satisfied a key condition for surrogacy. These results highlight that preclinically it is very challenging to find a surrogate marker based purely on measures of tumour burden.

scholarly journals Drug repurposing and polypharmacology to fight SARS-CoV-2 through the inhibition of the main protease

2020 ◽  
Author(s):  
Luca Pinzi ◽  
Annachiara Tinivella ◽  
Fabiana Caporuscio ◽  
Giulio Rastelli
Keyword(s):  
Clinical Trials ◽  
Antiviral Activity ◽  
Therapeutic Indication ◽  
Drug Repurposing ◽  
Drug Candidates ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Potential Inhibitors ◽  
Selection Of

Abstract Therapeutic options are urgently needed to fight the outbreak of a novel coronavirus (SARS-CoV-2), which causes the COVID-19 disease and is spreading rapidly around the world. Drug repurposing can significantly accelerate the identification of drug candidates suitable for clinical evaluation. Moreover, polypharmacological effects may increase antiviral activity and/or counteract severe complications concurrently affecting COVID-19 patients. Herein, we present the results of a computational drug repurposing campaign in search of potential inhibitors of the main protease of SARS-CoV-2. The screening allowed the selection of 22 promising drugs. Some of them have already entered clinical trials, but the vast majority of the identified compounds are new and have never been considered before. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

PILONIDAL DISEASE: CHANGES IN UNDERSTANDING OF ETIOLOGY, PATHOGENESIS AND APPROACH TO TREATMENT

2019 ◽  
Vol 72 (8) ◽  
pp. 1559-1565
Author(s):  
Viktor Konoplitskyi ◽  
Ruslan Shavliuk ◽  
Dmytro Dmytriiev ◽  
Kostiantyn Dmytriiev ◽  
Oleksii Kyrychenko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pilonidal Sinus ◽  
Randomized Clinical Trials ◽  
Web Of Science ◽  
Surgical Intervention ◽  
Pilonidal Disease ◽  
Treatment Methods ◽  
Principles Of Treatment ◽  
Selection Of

Data from Web of Science, SCOPUS, Pub Med, Medline, E-library, and other sources was used in writing this article. The main focus was directed towards literature written in English. The selection of literature was based on such concepts as: etiopathogenesis, historical principles of treatment, methods of surgical and non-surgical intervention. Data from metanalysis publications and randomized clinical trials pertaining to the treatment of the pilonidal sinus at various stages of its formation was used, as well.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

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