China
Africa
Explore chapters and articles related to this topic
Clinical Sequelae and Functional Outcomes
Published in Mark A. Mentzer, Mild Traumatic Brain Injury, 2020
While promising neuroprotective drugs have been effective in animal TBI models, all have failed to produce effective results during Phase II or III clinical trials. The failure of preclinical study to translate into clinical implementation suggests the need to revisit TBI animal models and therapeutic strategies (Centers for Disease Control Prevention; National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention, 2014). Areas requiring innovation include improved clinical trial design, optimization of therapeutic dosing and timing, determination of the effects of age, sex, and species or strains, and improvements in brain drug delivery (Xiong et al., 2013).
Document Preparation
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
This synopsis is in addition to the highlights called for by the regulation. The synopsis serves as an overview at the time the full report is being reviewed, but it also provides a ready source of reference in conjunction with reviews by other disciplines within the regulatory agency. For example, a clinical study report may wish to reference one of the pharmacological and toxicological reports as the basis for a particular protocol or the reason for carrying out a specific measurement. The medical reviewer need not read the entire preclinical study report if it is properly synopsized.
Preclinical Development of Antisense Oligonucleotide Therapeutics for Cancer: Regulatory Aspect
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Chang-Ho Ahn, Joseph J. DeGeorge
The life threatening nature of cancer can justify acceptance of increased risks of serious treatment toxicities, and raises different issues in the preclinical development of AS ODNs as oncologic drugs compared to development of AS ODNs for non-oncologic indications. For example, genotoxicity tests are considered important for AS ODN drugs prior to phase I clinical studies when healthy normal volunteers will be entered in the study, an uncommon clinical development plan for anticancer therapies (Food and Drug Administration, 1996a). The design and timing of the preclinical studies are determined by the nature and the phase of the clinical studies proposed and the proposed cancer patient population. The most appropriate test species, a range of doses and a dosing schedule of the AS ODN, however, may be determined based on the targeted sequence of an AS ODN and initial pharmacology and pharmacokinetic studies. The duration of initial preclinical studies should be based on the duration of the drug treatment period of the proposed clinical studies. However, preclinical study durations longer than twenty-eight days are uncommon in support of treatment for advanced malignancies. A similar strategy is applicable to develop AS ODNs to treat advanced malignancies.
Synthetic engineered bacteria for cancer therapy
Published in Expert Opinion on Drug Delivery, 2023
Preclinical animal studies are a prerequisite process before moving the bacteriotherapy targeting cancer into a clinical trial. In this process, the choice of suitable bacteria strains and animal models are two major considerations. Several bacteria strains such as S. typhimurium and Listeria monocytogenes are being evaluated in a clinical trial (Table 4) due to their positive results in preclinical studies [45,173]. For example, researchers from McGill University are conducting a phase ll clinical trial using the genetically engineered S. typhimurium strain that expresses IL-2 to treat metastatic pancreatic cancer (NCT04589234; Table 4). The same strain was also used in other clinical trials to treat different tumors, including neuroblastoma, myeloma, and glioblastoma. Furthermore, the tumor targeting colonization ability of bacteria such as Listeria monocytogenes can be different due to the heterogeneity in tumor structures and immune systems across species [174,175]. Consequently, the preclinical study result may be different from the clinical trial outcomes. Therefore, the invention of novel therapeutic agents as well as bacterial engineering methods must urgently address these limitations soon to successfully develop more bacteriotherapy strategies that can be widely used clinically.
Animal models of Huntington’s disease and their applicability to novel drug discovery and development
Published in Expert Opinion on Drug Discovery, 2023
Shubham Upadhayay, Sumit Jamwal, Puneet Kumar
In the drug discovery process, the preclinical study is very crucial that makes a substantial contribution to the investigation of new therapies, as the results from the preclinical phase decide whether to proceed for clinical trials in humans or not. No doubt, animals (small or large) have made a substantial contribution to drug discovery and development for HD [26,39]. Investigation focuses on reducing the excessive aggregation of HTT protein by testing new synthetic drugs or naturally occurring antioxidants/and repurposing drugs using a transgenic or toxin-based rodent model. In this series, several drugs such as genistein and 17β-estradiol [60], rutin [51], thymoquinone [59], and olesoximer [69] showed potential effects through reducing the aggregation and enhancing the cleavage of mHTT [93]. In addition to this, several preclinical studies are focused on testing cystamine, meclizine, and eicosapentaenoic acid for their potential neuroprotective effect on mitochondrial dysfunctioning. Moreover, targeting transcriptional dysregulation by employing the use of histone deacetylase inhibitor, i.e. sodium phenylbutyrate, HDACi4b, SAHA, mithramycin, and chromomycin showed notable neuroprotection in rodent models [94].
Effects of topical prostaglandin drops on angiogenesis in an in ovo chick chorioallantoic membrane model
Published in Cutaneous and Ocular Toxicology, 2021
Mehmet Cem Sabaner, Resat Duman, Ayhan Vurmaz, Tolga Ertekin
The preclinical study has several limitations. First, is the small sample size of each group (n: 10). Second, the prostaglandin drops used in this research contained preservatives such as benzalkonium chloride (bimatoprost and latanoprost) or polyquaternium-1 (travoprost). The use of preservatives may slightly alter the results. Third, is non-specific inflammatory reactions that can develop due to the CAM model. Lastly, is the image analysis program used as semi-automatic and manual. This situation was tried to be solved by blind multiple researchers’ evaluation. It is also known that a 95% confidence interval is not only used for statistical significance, but also applies to biological significance. However, more efficient results can be obtained with a fully automated analysis program. Thus, appropriate further studies are needed without preservatives, with a higher sample size and different image analysis programs recommended.