scholarly journals Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Sweta Shah ◽  
Marc Marie Dooms ◽  
Sofia Amaral-Garcia ◽  
Mariana Igoillo-Esteve
Keyword(s):  
Rare Diseases ◽  
Neurodegenerative Disorders ◽  
Low Frequency ◽  
Drug Repurposing ◽  
Wolfram Syndrome ◽  
Pharmaceutical Companies ◽  
Time Saving ◽  
Life Threatening ◽  
Repurposed Drugs

Rare diseases are life-threatening or chronically debilitating low-prevalent disorders caused by pathogenic mutations or particular environmental insults. Due to their high complexity and low frequency, important gaps still exist in their prevention, diagnosis, and treatment. Since new drug discovery is a very costly and time-consuming process, leading pharmaceutical companies show relatively low interest in orphan drug research and development due to the high cost of investments compared to the low market return of the product. Drug repurposing–based approaches appear then as cost- and time-saving strategies for the development of therapeutic opportunities for rare diseases. In this article, we discuss the scientific, regulatory, and economic aspects of the development of repurposed drugs for the treatment of rare neurodegenerative disorders with a particular focus on Huntington’s disease, Friedreich’s ataxia, Wolfram syndrome, and amyotrophic lateral sclerosis. The role of academia, pharmaceutical companies, patient associations, and foundations in the identification of candidate compounds and their preclinical and clinical evaluation will also be discussed.

scholarly journals From Off-Label to Repurposed Drug in Non-Oncological Rare Diseases: Definition and State of the Art in Selected EU Countries

2017 ◽  
Vol 1 ◽  
pp. maapoc.0000016 ◽  
Author(s):  
Paola Minghetti ◽  
Elena P. Lanati ◽  
Josie Godfrey ◽  
Oriol Solà-Morales ◽  
Olivier Wong ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Drug Repurposing ◽  
Orphan Drugs ◽  
New Drugs ◽  
Success Rates ◽  
Great Opportunity ◽  
Off Label ◽  
Research Activities ◽  
Oncological Diseases ◽  
Repurposed Drugs

Introduction Almost 8,000 rare diseases exist worldwide, affecting approximately 350 million people. Nevertheless, only 5% receive a specific authorized or licensed treatment. The need for effective and rapidly available therapies is still unmet for many patients. Objective The objective is to define repurposing versus off-label drugs, and to evaluate pathways of repurposed drugs for rare non-oncological diseases in Italy, France, England, and Spain (the EU4 countries). Methods This original paper is based on 3 research activities: (i) a nonsystematic literature research; (ii) a questionnaire-based survey to regulatory experts; and (iii) research on approval timelines and therapy prices of repurposed non-oncology orphan drugs. Official approval dates in England are not available if the National Institute for Health and Care Excellence does not appraise the products. Results Only France provides a specific adaptive pathway from off-label to repurposed drugs. Pricing and reimbursement assessment for the drug samples varied across the EU4 countries: time-to-market for repurposed drugs versus new drugs is longer in all analyzed countries; that is, 979 days versus 462 days in Italy, 502 days versus 350 days in France, and 624 versus 378 days in Spain. Repurposed drugs have higher success rates from development to approval than novel drugs (30% vs. 11%). Small- and medium-sized enterprises owned 9 of 12 repurposed non-oncology orphan drugs, of which only 4 were reimbursed in all EU4 countries. Prices were more homogeneous across EU4 although the reimbursement rates were different. Conclusions Drug repurposing represents a great opportunity to treat rare non-oncological diseases. However, a more homogenous assessment across EU4 could ensure reimbursement and prices high enough to reward organizations investing in this field.

scholarly journals Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1603
Author(s):  
Adrian Mor ◽  
Anna Tankiewicz-Kwedlo ◽  
Anna Krupa ◽  
Dariusz Pawlak
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Kynurenine Pathway ◽  
Mitochondrial Damage ◽  
Oxidative Metabolites ◽  
Oxidative Stress Level ◽  
Life Threatening ◽  
Proinflammatory Factors

Neurodegenerative disorders are chronic and life-threatening conditions negatively affecting the quality of patients’ lives. They often have a genetic background, but oxidative stress and mitochondrial damage seem to be at least partly responsible for their development. Recent reports indicate that the activation of the kynurenine pathway (KP), caused by an activation of proinflammatory factors accompanying neurodegenerative processes, leads to the accumulation of its neuroactive and pro-oxidative metabolites. This leads to an increase in the oxidative stress level, which increases mitochondrial damage, and disrupts the cellular energy metabolism. This significantly reduces viability and impairs the proper functioning of central nervous system cells and may aggravate symptoms of many psychiatric and neurodegenerative disorders. This suggests that the modulation of KP activity could be effective in alleviating these symptoms. Numerous reports indicate that tryptophan supplementation, inhibition of KP enzymes, and administration or analogs of KP metabolites show promising results in the management of neurodegenerative disorders in animal models. This review gathers and systematizes the knowledge concerning the role of metabolites and enzymes of the KP in the development of oxidative damage within brain cells during neurodegenerative disorders and potential strategies that could reduce the severity of this process.

Protective role of anticancer drugs in neurodegenerative disorders: A drug repurposing approach

2020 ◽  
Vol 140 ◽  
pp. 104841
Author(s):  
Dia Advani ◽  
Rohan Gupta ◽  
Rahul Tripathi ◽  
Sudhanshu Sharma ◽  
Rashmi K. Ambasta ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Neurodegenerative Disorders ◽  
Drug Repurposing ◽  
Protective Role

scholarly journals Drug Repurposing: A Paradigm Shift in Drug Discovery

2020 ◽  
Vol 5 (04) ◽  
pp. 60-68
Author(s):  
Saravanan Jayaram ◽  
Emdormi Rymbai ◽  
Deepa Sugumar ◽  
Divakar Selvaraj
Keyword(s):  
Drug Discovery ◽  
Success Rate ◽  
Chemical Structure ◽  
Target Identification ◽  
Drug Repurposing ◽  
New Drugs ◽  
Attractive Option ◽  
Traditional Drug ◽  
Repurposed Drugs

The traditional methods of drug discovery and drug development are a tedious, complex, and costly process. Target identification, target validation; lead identification; and lead optimization are a lengthy and unreliable process that further complicates the discovery of new drugs. A study of more than 15 years reports that the success rate in the discovery of new drugs in the fields of ophthalmology, cardiovascular, infectious disease, and oncology to be 32.6%, 25.5%, 25.2% and 3.4%, respectively. A tedious and costly process coupled with a very low success rate makes the traditional drug discovery a less attractive option. Therefore, an alternative to traditional drug discovery is drug repurposing, a process in which already existing drugs are repurposed for conditions other than which were originally intended. Typical examples of repurposed drugs are thalidomide, sildenafil, memantine, mirtazapine, mifepristone, etc. In recent times, several databases have been developed to hasten drug repurposing based on the side effect profile, the similarity of chemical structure, and target site. This work reviews the pivotal role of drug repurposing in drug discovery and the databases currently available for drug repurposing.

scholarly journals The Role of Immunogenetics in COVID-19

2021 ◽  
Vol 22 (5) ◽  
pp. 2636
Author(s):  
Fanny Pojero ◽  
Giuseppina Candore ◽  
Calogero Caruso ◽  
Danilo Di Bona ◽  
David A. Groneberg ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
Drug Repurposing ◽  
Future Research ◽  
Life Threatening ◽  
History Of ◽  
Treatment Plans ◽  
And Function

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.

Are Three Items Sufficient to Measure Sense of Coherence?

2018 ◽  
Vol 34 (4) ◽  
pp. 229-237 ◽  
Author(s):  
Francesca Chiesi ◽  
Andrea Bonacchi ◽  
Caterina Primi ◽  
Alessandro Toccafondi ◽  
Guido Miccinesi
Keyword(s):  
Sense Of Coherence ◽  
Convergent Validity ◽  
Clinical Sample ◽  
Clinical Samples ◽  
Depression Symptoms ◽  
Time Saving ◽  
Positive Role ◽  
Patients With Cancer ◽  
Measure Sense

Abstract. The present study aimed at evaluating if the three-item sense of coherence (SOC) scale developed by Lundberg and Nystrom Peck (1995) can be effectively used for research purpose in both nonclinical and clinical samples. To provide evidence that it represents adequately the measured construct we tested its validity in a nonclinical (N = 658) and clinical sample (N = 764 patients with cancer). Results obtained in the nonclinical sample attested a positive relation of SOC – as measured by the three-item SOC scale – with Antonovsky’s 13-item and 29-item SOC scales (convergent validity), and with dispositional optimism, sense of mastery, anxiety, and depression symptoms (concurrent validity). Results obtained in the clinical sample confirmed the criterion validity of the scale attesting the positive role of SOC – as measured by the three-item SOC scale – on the person’s capacity to respond to illness and treatment. The current study provides evidence that the three-item SOC scale is a valid, low-loading, and time-saving instrument for research purposes on large sample.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

Calculation-and-experimental estimation of the role of the frequency ratio in changing the endurance at two-frequency deformation modes

2019 ◽  
Vol 85 (1(I)) ◽  
pp. 64-71 ◽  
Author(s):  
M. M. Gadenin
Keyword(s):  
High Frequency ◽  
Experimental Studies ◽  
Low Frequency ◽  
Reduction Factor ◽  
Single Frequency ◽  
Cyclic Loads ◽  
Small Ratio ◽  
Harmonic Components ◽  
Deformation Modes

The cycle configuration at two-frequency loading regimes depends on the number of parameters including the absolute values of the frequencies and amplitudes of the low-frequency and high-frequency loads added during this mode, the ratio of their frequencies and amplitudes, as well as the phase shift between these harmonic components, the latter having a significant effect only with a small ratio of frequencies. Presence of such two-frequency regimes or service loading conditions for parts of machines and structures schematized by them can significantly reduce their endurance. Using the results of experimental studies of changes in the endurance of a two-frequency loading of specimens of cyclically stable, cyclically softened and cyclically hardened steels under rigid conditions we have shown that decrease in the endurance under the aforementioned conditions depends on the ratio of frequencies and amplitudes of operation low-frequency low-cycle and high-frequency vibration stresses, and, moreover, the higher the level of the ratios of amplitudes and frequencies of those stacked harmonic processes of loading the greater the effect. It is shown that estimation of such a decrease in the endurance compared to a single frequency loading equal in the total stress (strains) amplitudes can be carried out using an exponential expression coupling those endurances through a parameter (reduction factor) containing the ratio of frequencies and amplitudes of operation cyclic loads and characteristic of the material. The reduction is illustrated by a set of calculation-experimental curves on the corresponding diagrams for each of the considered types of materials and compared with the experimental data.

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