Translational Safety Genetics

Bhoumik, Priyasma; Río-Espínola, Alberto Del; Hahne, Florian; Moggs, Jonathan G.; Grenet, Olivier

doi:10.1177/0192623316675064

Cited by 6 publications

(5 citation statements)

References 70 publications

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“…When choosing a model system to study target-related safety aspects, the likely cross-species translation of these toxicities must be considered. Sometimes, genes are only expressed in disease states or are not present/functional in the selected preclinical species 93,94 . Moreover, the organotypic quality of the model can be critical 95 .…”

Section: Human and Cross-species Translatabilitymentioning

confidence: 99%

Improving target assessment in biomedical research: the GOT-IT recommendations

Emmerich¹,

Martínez-Gamboa

Hofmann

et al. 2020

Nat Rev Drug Discov

110

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Academic research plays a key role in identifying new drug targets, including understanding target biology and links between targets and disease states. To lead to new drugs, however, research must progress from purely academic exploration to the initiation of efforts to identify and test a drug candidate in clinical trials, which are typically conducted by the biopharma industry. This transition can be facilitated by a timely focus on target assessment aspects such as target-related safety issues, druggability and assayability, as well as the potential for target modulation to achieve differentiation from established therapies. Here, we present recommendations from the GOT-IT working group, which have been designed to support academic scientists and funders of translational research in identifying and prioritizing target assessment activities and in defining a critical path to reach scientific goals as well as goals related to licensing, partnering with industry or initiating clinical development programmes. Based on sets of guiding questions for different areas of target assessment, the GOT-IT framework is intended to stimulate academic scientists’ awareness of factors that make translational research more robust and efficient, and to facilitate academia–industry collaboration.

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Section: Human and Cross-species Translatabilitymentioning

confidence: 99%

Improving target assessment in biomedical research: the GOT-IT recommendations

Emmerich¹,

Martínez-Gamboa

Hofmann

et al. 2020

Nat Rev Drug Discov

110

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“…In this, mouse genetic data such as knockouts and overexpression are very useful for novel targets, depending on whether the intention is drug-target inhibition or activation. 11,12 Similarly, human genetic conditions where the intended target is deleted or modified can give insight into the likely outcomes of target modulation; several databases such as OMIM 13 and recent advances in GWAS have been used to support target safety by leveraging human genetic data. 14 Animal and clinical data from previous drugs that interact with the target might exist for more mature targets especially if the drug has reached the market and the drug approval information is in the public domain.…”

Section: Generating a Tsamentioning

confidence: 99%

Data science in drug discovery safety: Challenges and opportunities

Coltman,

Roberts,

Sidaway

2023

Exp Biol Med (Maywood)

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Early de-risking of drug targets and chemistry is essential to provide drug projects with the best chance of success. Target safety assessments (TSAs) use target biology, gene and protein expression data, genetic information from humans and animals, and competitor compound intelligence to understand the potential safety risks associated with modulating a drug target. However, there is a vast amount of information, updated daily that must be considered for each TSA. We have developed a data science–based approach that allows acquisition of relevant evidence for an optimal TSA. This is built on expert-led conventional and artificial intelligence–based mining of literature and other bioinformatics databases. Potential safety risks are identified according to an evidence framework, adjusted to the degree of target novelty. Expert knowledge is necessary to interpret the evidence and to take account of the nuances of drug safety, the modality, and the intended patient population for each TSA within each project. Overall, TSAs take full advantage of the most recent developments in data science and can be used within drug projects to identify and mitigate risks, helping with informed decision-making and resource management. These approaches should be used in the earliest stages of a drug project to guide decisions such as target selection, discovery chemistry options, in vitro assay choice, and end points for investigative in vivo studies.

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“…There is no guidance what animal origin is preferred for the safety assessment of products, but it is recognized that variation between animals from different geographic origins can contribute to diverse drug pharmacologic and toxicologic responses. 36 The question if geographical origin of NHPs matters is typically answered by comparing baseline data between animal cohorts of different geographical origin. Unfortunately, investigations that explicitly evaluate such difference in the context of a regulatory general toxicity study are extremely scarce.…”

Section: Geographical Origin Of Long-tailed Macaques Used In General ...mentioning

confidence: 99%

Section: Geographical Origin Of Long-tailed Macaques Used In General ...mentioning

confidence: 99%

Does Geographical Origin of Long-Tailed Macaques (Macaca fascicularis) Matter in Drug Safety Assessment?: A Literature Review and Proposed Conclusion

Weinbauer¹,

Mecklenburg²

2022

Toxicol Pathol

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Long-tailed macaques are the predominant nonhuman primate species for the nonclinical safety testing of biopharmaceuticals. This species comprises 9 subspecies with Macaca fascicularis fascicularis naturally occurring in Southeast Asia. Since the 17th century, M. f. fascicularis also occurs on Mauritius. Cynomolgus macaques do not naturally occur in China, but are bred in many farms across the country. The current shortage in animal supply raises the question whether geographical animal origin matters and if animals from different geographical regions can be combined on a drug development program or even a single experiment. This article reviews geographical animal origin in relation to selected endpoints that are relevant in nonclinical drug safety testing. Animals from different countries within Asia mainland do not appear to show any meaningful difference. Very little data are available for animals from Asia island. Mauritian animals show consistent differences from Asian animals in several clinical and anatomical pathology parameters. For developmental parameters, animals from Mauritius and Asia are comparable with the exception that Mauritian animals mature faster. In the authors’ view, differences between the geographical clusters can be accounted for as long as baseline and reference data are available.

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Translational Safety Genetics

Cited by 6 publications

References 70 publications

Improving target assessment in biomedical research: the GOT-IT recommendations

Improving target assessment in biomedical research: the GOT-IT recommendations

Data science in drug discovery safety: Challenges and opportunities

Does Geographical Origin of Long-Tailed Macaques (Macaca fascicularis) Matter in Drug Safety Assessment?: A Literature Review and Proposed Conclusion

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