Metabolomics study heralds change in animal testing


unreliable, the majority of new chemical grouping and read-across submissions are rejected by the European Chemicals Agency (ECHA).


The study from the MATCHING consortium, funded by the European Chemical Industry Council’s Long-Range Research Initiative (Cefic-LRI) was carried out in partnership with BASF, BASF Metabolome Solutions, ECHA, Imperial College London, Syngenta, Vrije Universiteit Amsterdam and the US Environmental Protection Agency.


Mark Viant, Professor of Metabolomics at the University of Birmingham explained: “Chemicals fall into three categories of drugs, pesticides and industrial chemicals and we are exposed to some of these every single day of our lives. Industrial chemicals are not intended for direct exposure to humans or the environment, but inevitably this will happen, so the toxicology information must be accurate.


“Instead of only measuring the structural similarity of the chemicals to form groups, we have found that by using metabolomics to measure the biological responses of the chemicals, we can make the grouping and read across more reliable.”


Mark Viant (Credit: University of Birmingham)


The University of Birmingham is leading an international collaboration that has used metabolomics as a robust method to assess safety of chemicals, which is also raising hopes for a reduction in animal testing procedures.


Grouping and read-across, an EU-approved approach, allows toxicology information from already approved chemicals to be copied across to new structurally similar substances, enabling them to be brought forward for market approval. However, because this process is


To test the effectiveness of metabolomics, six independent laboratories were sent common plasma samples from rats which had been tested with eight chemicals. The teams did not know what the chemicals were and had to correctly group them by looking for diagnostic metabolic biomarkers. By using a ‘shotgun approach’ like metabolomics, scientists could measure thousands of markers like amino acids and lipids, using mass spectrometry. This helped the labs group the eight chemicals into two groups of three and one of two chemicals.


All results were then sent to the European Chemicals Agency who compiled them before the findings were


revealed to the whole consortium. The five labs whose data passed quality control all discovered the same grouping. This is the first time that the use of metabolomics for grouping has been proven to be a reproducible method.


Katherine Santizo from Cefic-LRI: “This is a massive step forward to improve the existing grouping and read-across approach. The fact that five labs from different countries all got the same, correct results while using different methods and instruments, their own procedures and statistical analysis shows that metabolomics is a reliable method.”


Professor Viant added that rats were ‘not good models for humans’ with reproducibility of results also ‘not great’ and that even without the ethical considerations, this approach was both a costly and slow process. “So, by making the grouping and read-across approach more robust by using metabolomics, the number of lab rats being tested could be dramatically cut,” he pointed out.


Tomasz Sobanski, Team Leader for Alternative Methods in the Computational Assessment and Alternative Methods Unit, ECHA said: “The need to demonstrate the reliability of metabolomics was first identified during one of our workshops in 2016. We are very impressed with the results of this research and we believe that they will improve the grouping and read-across. We hope that learnings from this research will be included in new guidance for the chemical industry to allow commercial laboratories to provide these services widely.”


The study was published in Archives in Toxicology. More information online: ilmt.co/PL/wzdj


62271pr@reply-direct.com


Dundee’s CeTPD joins global fight against childhood cancer


The University of Dundee’s Centre for Targeted Protein Degradation (CeTPD) is contributing in a global effort to explore new means of tackling solid tumours in children. CeTPD director Professor Alessio Ciulli will be part of the Cancer Grand Challenges KOODAC team, which brings together clinicians, advocates and scientists with expertise in structural biology, chemical biology, paediatric oncology and medicinal chemistry, across ten institutions and five countries.


The Cancer Grand Challenges Initiative, founded in 2020 by Cancer Research UK and the National Cancer Institute in the US, will fund five teams for five years with sums of up to $25 million each. Team KOODAC will be supported by Cancer Research UK, Institut National Du Cancer and KiKa (Children Cancer Free Foundation).


A leading cause of death due to disease among children globally, outcomes for some childhood cancers have not improved in more than 30 years. Treatments for solid tumours in children still rely on decades-old chemotherapies and often radiotherapy.


Team KOODAC will be using protein degradation strategies to target previously undruggable drivers of children’s


cancers. Any drug that might emerge has the potential to transform the lives of those affected by that particular cancer type.


Professor Ciulli said: “We were honoured to be invited and immediately felt a sense of purpose, a strong focus on team science and realised the unique opportunity and call ahead of us. Revolutionising paediatric solid tumour treatment demands global collaboration in the face of persisting outdated therapies.


“We have assembled a team with unrivalled technology and expertise to realise our ambitious goal of driving innovation in targeted paediatric cancer therapeutics. Our vision is to pioneer drugs that will become the new standards of care for children with oncoprotein-driven solid malignancies.”


Dr David Scott, Director of Cancer Grand Challenges, added: “Together with our network of visionary partners and research leaders, Cancer Grand Challenges unites the world’s brightest minds across boundaries and disciplines and aims to overcome cancer’s toughest problems.


“With this investment, our largest to date, we continue to grow our global research community and fund new teams


Alessio Ciulli (Credit: University of Dundee)


that have the potential to surface discoveries that could positively impact cancer outcomes.”


More information online: ilmt.co/PL/5B28 62272pr@reply-direct.com


Collaboration to broaden understanding of Alzhemer’s diseases


understanding of AD mechanisms in order to identify those more at risk of developing the disease and enable provision of appropriate interventions much earlier in the disease pathology.


Brain scan (Credit: Sheffield Hallum University)


Sheffield Hallam University and clinical stage pharmaceutical company PharmaKure have entered into a partnership that will focus on gene-based environmental biomarkers, or epigenetic markers, for calculating risk scores for Alzheimer’s diseases (AD).


The collaborative study, which will use the company’s ALZmetrixTM


blood-based biomarker aims to gain a better


Professor Gavin Reynolds, Biomolecular Sciences Research Centre, Sheffield Hallam University, who has published over 300 papers on the pathology of neurotransmitter systems involved in psychiatric disorders and now focuses on epigenetics effects in neuro diseases explained: “We have been working on the relationship of environmental stresses with respect to brain diseases. Our genes are coded in our DNA, but epigenetics looks at how the cell turns genes on and off according to different environmental exposure, such as the aging process, stress, trauma etc. We want to identify abnormal epigenetic changes associated with brain diseases and these changes may be modifiable with medications.”


Dr Helene Fachim, Neuroscientist, PharmaKure, said: “Mental health and the environment can both contribute to the development of brain diseases. Influences, such as trauma and chronic stress, can bring about epigenetic changes to DNA that may result in a range of psychiatric and neurological disorders. We are therefore looking for epigenetic factors that are specifically related to Alzheimer’s Disease.”


“We would like to use these epigenetic approaches for a better understanding of AD, so that we can stratify a person’s risk of developing it. Then, we could act in preventive ways, or administer AD drugs earlier in life when they are more effective.”


AD is a multifactorial disease and it is known that environmental factors can make an important contribution to triggering it. The study’s main hypothesis is that there is differential methylation in certain target genes related to AD compared to non-AD controls. If this hypothesis proves to be true, Pharmakure can start the validation of an epigenetic predictive risk score for cognitive impairment and AD.


“We are very positive and excited about this new epigenetics collaboration and we believe that bringing together academia and industry is the best way to achieve our goals. We are looking forward to sharing important results in the near future,” said Dr. Farid Khan, CEO, PharmaKure.


More information online: ilmt.co/PL/1AWE 62275pr@reply-direct.com


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68