|
Can we panelise seizure? Toxicological Sciences, Online ahead of publication
|
Seizure liability remains a significant cause of attrition in drug discovery and development, leading to loss of competitiveness, delays, and increased costs. Current detection methods rely on observations made in in vivo studies intended to support clinical trials, such as tremors or other abnormal movements. These signs could be missed or misinterpreted; thus, definitive confirmation of drug-induced seizure requires a follow-up electroencephalogram study…
|
Roberts, RA, Authier, S, Mellon, D, Morton, M, Suzuki, I, Tjalkens, RB, Valentin, J-P and Pierson, J (2020)
|
Link
|
|
Justification for species selection for pharmaceutical toxicity studies. Toxicology Research
|
Toxicity studies using mammalian species are generally required to provide safety data to support clinical development and licencing registration for potential new pharmaceuticals…
|
Helen Prior, Richard Haworth, Briony Labram, Ruth Roberts, Alison Wolfreys and Fiona Sewell (2020)
|
Link
|
|
Advancing Genomics for Rare Disease Diagnosis and Therapy Development. Frontiers in Pharmacology 11, 1523.
|
Rare diseases affect only a small percentage of the population and are often chronic and potentially life-threatening. There are more than 7,000 known rare diseases, and yet fewer than 700 approved treatment options are available. Progress made with the use of emerging technologies such as next-generation sequencing (NGS) and bioengineering holds great promise in advancing rare disease diagnosis and therapy development
|
Liu, Z, Roberts, R, Shi, T, Mikailov, M and Tong, W (2020)
|
Link
|
|
Opportunities for use of one species for longer-term toxicology testing during drug development: A cross-industry evaluation. Reg Tox Pharm. 113, 104624.
|
An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within regulatory general toxicology studies…
|
Prior et al (2020)
|
Link
|
|
Drug Repositioning for Noonan and LEOPARD Syndromes by Integrating Transcriptomics With a Structure-Based Approach. Frontiers in Pharmacology, 11, 927.
|
Noonan and LEOPARD syndromes (NS and LS) belong to a group of related disorders called RASopathies characterized by abnormalities of multiple organs and systems including hypertrophic cardiomyopathy and dysmorphic facial features. There are no approved drugs for these two rare diseases, but it is known that a missense mutation in PTPN11 genes is associated with approximately 50% and 70% of NS and LS cases, respectively…
|
Zhu, L, Roberts, R, Huang, R, Zhao, J, Xia, M, Delavan, B, Mikailov, M, Tong, W, and Liu, Z. (2020)
|
Link
|
|
Innovative models for in vitro detection of seizure. Toxicology Research 8 (6), 784-788.
|
Data show that toxicity to the central nervous system (CNS) is the most frequent cause of safety failures during the clinical phase of drug development. CNS endpoints such as seizure pose a safety risk to patients and volunteers and can lead to a loss of competitiveness, delays, and increased costs. Current methods rely on detection in the nonclinical rodent and non-rodent studies required to support clinical trials. There are two main issues with this approach; seizure may be missed in the animal studies and, even if seizure is detected, significant resource has already been invested in the project by this stage…
|
Rockley, K, Morton M and Roberts, R (2019)
|
Link
|
|
Towards Clinical Implementation of Next Generation Sequencing-based Genetic Testing in Rare Diseases: Where are we? Trends in Genetics. 45, 678-680.
|
Next-generation sequencing (NGS) technologies have changed the landscape of genetic testing in rare diseases. However, the rapid evolution of NGS technologies has outpaced its clinical adoption. Here, we re-evaluate the critical steps in the clinical application of NGS-based genetic testing from an informatics perspective. We suggest a ‘fit-for-purpose’ triage of current NGS technologies…
|
Liu, Z, Zhu, L, Roberts, RA and Tong, W (2019)
|
Link
|
|
Drug Discovery and Development: biomarkers of neurotoxicity and neurodegeneration. Experimental Biology and Medicine. 243: 1037–1045
|
The discovery and development of new drugs are vital if we are to improve and expand treatment options available to improve outcomes for patients. Overall, therapeutic strategies fall into two broad categories: small molecules and biologics, although more recently there has been a growth in novel platforms such as miRNAs and oligonucleotides. On average, the development of a small molecule drug takes around 12 years and costs around $50m. Despite this huge investment of time and money, attrition remains a major challenge and very few molecules actually make it through to the market…
|
Walker, A, Imam, S and Roberts, RA (2018).
|
Link
|
|
Understanding drug targets: there’s no such thing as bad news. Drug Discovery Today, 23, 1925-1928.
|
How can small-to-medium pharma and biotech companies enhance the chances of running a successful drug project and maximise the return on a limited number of assets? Having a full appreciation of the safety risks associated with proposed drug targets is a crucial element in understanding the unwanted side-effects that might stop a project in its tracks. Having this information is necessary to complement knowledge about the probable efficacy of a future drug…
|
Roberts, RA (2018)
|
Link
|
|
The Liver Toxicity Knowledge Base (LKTB) and Drug-Induced Liver Injury (DILI) Classification for Assessment of Human Liver Injury. Expert review of Gastroenterology and Hepatology. 12, 31-38.
|
Introduction: Drug-induced liver injury (DILI) is challenging for drug development, clinical practice and regulation. The Liver Toxicity Knowledge Base (LTKB) provides essential data for DILI study.
Areas covered: The LTKB provided various types of data that can be used to assess and predict DILI. Among much information available, several reference drug lists with annotated human DILI risk are of important…
|
Thakkar, S, Chen, M, Fang, H, Liu, Z, Roberts, R, Tong, W (2018).
|
Link
|
|
Computational Drug Repositioning for Rare Diseases in the era of Precision Medicine. Drug Discovery Today, 2, 382-394.
|
There are tremendous unmet needs in drug development for rare diseases. Computational drug repositioning is a promising approach and has been successfully applied to the development of treatments for diseases. However, how to utilize this knowledge and effectively conduct and implement computational drug repositioning approaches for rare disease therapies is still an open issue. Here, we focus on the means of utilizing accumulated genomic data for accelerating and facilitating drug repositioning for rare diseases…
|
Delavan, B, Roberts, R, Goldsmith, J, Fang, H, Thakkar, S, Huang, R, Bao, W, Tong, W and Liu, Z (2018).
|
Link
|
|
Lessons learned from two decades of anticancer drugs. TiPS 38, 852-872.
|
Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena…
|
Liu, Z, Delavan, B, Roberts, R and Tong, W (2017).
|
Link
|