Professor Chaozong Liu is leading a Rosetrees Trust-funded project, with postdoctoral research associate Dr. Maryam Tamaddon, to investigate a tissue engineering approach for the treatment of cartilage damage, as a result of repetitive injuries or osteoarthritis.
Based at UCL Institute of Musculoskeletal and Orthopaedic Sciences, the team have already developed a novel ex vivo bone plug model for evaluating scaffold technology in order to speed up translation of this technology into clinical practice. They have also demonstrated improved mechanical and biological parameters in various model systems, both in vitro and in vivo.
Dr. Maryam Tamaddon
The team have recently received ethical approval to access young patients’ tissue for use in their project. “This is an important step because there is variability between children and adults for this type of study, and children are currently under-investigated. This allows the researchers to understand the osteoarthritis development at early stage”, as quoted by Dr. Maryam Tamaddon.
Significantly, a Phase I clinical trial has been agreed to start in October 2019, with a cohort of 20 patients. This will take place at the Royal National Orthopaedic Hospital, NHS Trust, for patients with knee joint cartilage damage. Safety is being considered as the primary outcome. The results from this trial will be relevant to clinicians, because this will offer a new treatment option for treatment of cartilage damage.
Professor Chaozong Liu
Once the Phase I clinical trial has begun, this will facilitate subsequent running of other trials in parallel and recruitment of more patients.
Professor Chaozong Liu from University College London, who is leading this research, commented, “We have demonstrated that the novel Bone Plug Model, developed under a Rosetrees Trust award, is able to provide more relevant human tissue-scaffold interactions, and speed up the translation of novel technology into clinical practice. We are very happy with the achievement and very grateful for Rosetrees Trust for supporting our work.”
Dr. Williams-Gray is a Rosetrees Trust-funded researcher based at the University of Cambridge, who is leading a team that is currently investigating the role of Toll-like receptors in brain inflammation and disease progression in Parkinson’s disease and its associated dementia. The team are using human post-mortem tissue from patients with Parkinson’s to explore the relationship between pathological changes and clinical course of the disease. In addition, they are using a novel laboratory-based model of Parkinson’s disease which will allow them to determine how Toll-like receptor blocking drugs will affect the inflammatory response and consequent nerve cell damage.
A recent review of Toll-like receptors in Parkinson’s disease and alpha-synucleinopathies, published by Dr. Caroline Williams-Gray and her team, supports the idea that these receptors may have potential as therapeutic targets. In their review, they have highlighted that there is increased interest in using treatments aimed at either preventing or stopping brain inflammation in these diseases.
“Toll-like receptors are critical for the activation of immune cells and inflammation in the brain – and evidence that they play a role in Parkinson’s disease is accumulating.” – Antonina Kouli (Postdoctoral Research Associate, University of Cambridge)
Dr. Williams-Gray’s group also studies immune activation and inflammation in the blood in Parkinson’s disease patients. This work has implicated changes in immune cell types and function in Parkinson’s (Williams-Gray et al., 2018; Wijeyekoon et al., 2018; Scott et al., 2018), and has shown that patients who have more inflammation in the blood when they are diagnosed have more rapid progression of their disease (Williams-Gray et al., 2016). Their work to date on human post-mortem tissue confirms brain inflammation and specifically implicates Toll-like receptors in Parkinson’s disease and these findings will enhance our understanding of the neuropathological basis of Parkinson’s disease dementia, once published. Work is ongoing on the laboratory model, and due to complete in the next few months. If successful, this may pave the way for clinical trials of Toll-like receptor blocking drugs for use in the treatment of Parkinson’s disease.
“There is an urgent need to develop treatments that can halt or slow down the progression of Parkinson’s disease, as well as other neurodegenerative conditions which cause dementia. Suppressing brain inflammation is an exciting potential strategy which may be relevant to many of these diseases, and Toll-like receptors may provide a specific therapeutic target.” – Caroline Williams-Gray (Senior Clinical Research Associate, University of Cambridge & Honorary Consultant Neurologist, Cambridge University Hospitals NHS Foundation Trust)
Dr. Tina Chowdhury is a Rosetrees Trust-funded researcher, leading a team of scientists in the field of regenerative medicine. She is based at the Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, where she also plays an active role in science communication and public engagement alongside her academic roles.
Having recently given an exciting talk about saving babies’ lives, Dr. Chowdhury continues to inspire the next generation promoting subjects in STEAMM to young people at schools. The talk was chaired by Professor Brian Cox (OBE) who joined Dr. Chowdhury for a Question and Answer session. A short summary of her talk can be found on the Queen Mary University of London website.
Talk about saving babies’ lives inspires young people to become bioengineers
Dr. Chowdhury and her team, including Professor Anna David at UCL and Dr. David Barrett, have recently published the Rosetrees Trust-funded findings in Scientific Reports. This work was specifically about repairing fetal membranes to prevent preterm birth. A brief overview of the findings, can be found here on the Queen Mary University of London website.
You can also listen to the podcast from 12.15 where Tina was interviewed by Dr. Chris Smith, Naked Scientists.
This project has been very successful, generating five publications and one book chapter in total, as well as winning seven awards and prizes for the research. A project grant was awarded to Dr. Chowdhury and her collaborators from Great Ormond Street Hospital and Sparks children’s charities for the continuation of this work. Dr. Barrett achieved his PhD in March 2018, and worked as a Post-Doctoral Researcher funded by Sparks. Dr. Babatunde Okesola joined Tina’s team last month and is designing materials with nanotechnology to seal tears in fetal membrane defects.
In another Rosetrees Trust-funded project, Dr. Chowdhury and her team investigated a tissue engineering approach to repair defects in the windpipe of the unborn baby, using fetal stem cells. Studies from the PhD student working on this project, James Taylor, will contribute to a publication. This work will be important because of the particular emphasis on the novelty of using fetal-derived stem cells to generate chondrocytes.
Little Heartbeats is raising awareness for PPROM.
Dr. Chowdhury and her team are also receiving ongoing Rosetrees Trust funding for a project to heal fetal membrane defects and avoid preterm birth. This project combines technology in material chemistry, mechanobiology, biomechanics and imaging, to test therapies with fetal-on-a-chip mechanical models. The data obtained is in the early stages of this work and will be presented at the 23rd International Society for Prenatal Diagnosis and Therapy, Singapore in September 2019 and has been nominated for an Early Investigator award. This is a great opportunity for the PhD student working on this project, Eleni Costa, to showcase the latest findings from the team to leading experts in the field.
Here are a few words from Dr. Chowdhury: “In 2018, we established the Fetal Membrane Repair Network with a global community of scientists, clinicians, engineers, advocacy groups (Little Heartbeats) and children charities (Sparks, GOSH) to discuss ways to improve healing of the membranes after surgery or after the membranes rupture spontaneously. By working collaboratively with a multi-disciplinary team and by raising awareness about PPROM, we plan to develop a new clinical intervention that will improve healing, delay delivery and prevent preterm birth. We are very grateful to the Rosetrees Trust for supporting our research team and for inspiring the next generation of bioengineers.”
Antimicrobial resistance is recognised as the one of the gravest threats to global human health and is expected to kill more people than cancer by 2050. Therefore, new antibiotics are crucial. Rosetrees-funded research led by Dr. Ishwar Singh at Lincoln University has made, and continues to make, a significant contribution to the discovery and development of novel antibiotics. Currently, Dr. Singh is leading one of several teams around the world, in the fight against resistance, by developing teixobactin. This work was recently highlighted in the Guardian.
Dr. Ishwar Singh
Dr. Singh explained: “Antimicrobial resistance is spreading faster than the introduction of new antibiotics, which means there are major concerns about a possible health crisis. To tackle this global challenge, we are at the forefront of the development of 21st century antibiotics, teixobactins which kill multi-drug resistant bacterial pathogens such as MRSA.”
Teixobactin is exciting because it is a recently discovered natural compound, belonging to a new class of antibiotics and kills multi-drug resistant bacterial pathogens without detectable resistance. In his research, Dr. Singh aims to develop a library of simplified highly potent teixobactins to overcome the unmet clinical challenges in antimicrobial resistance. To achieve this, Dr. Singh will need to prepare, evaluate and gain mechanistic insights into the teixobactins he develops during this project.
In the long-term, this project can ultimately contribute to providing a new class of 21st century, clinically relevant, licensed antibiotics.
A Cambridge-led study, also known as the Next Generation Children’s Project, used progressive whole genome sequencing technology to help doctors identify and treat genetic conditions in babies and young children.
Professor Lucy Raymond
The study, led by Professors Lucy Raymond and David Rowitch, which is the largest of its kind to date, took blood samples from 350 babies and children in intensive care units with a variety of different conditions.
It was discovered that one in four babies used in the project had an underlying genetic condition that was then able to be more effectively treated from an early diagnosis. In fact, parents and doctors of these ill children received the test results from this project within two to three weeks on the NHS. The efficiency and accuracy of whole genome sequencing therefore paves the way for this kind of testing to be incorporated into conventional practice. Critically, this breakthrough will also have wider implications for parents who have lost a child for reasons that are not fully understood. It will be able to spare them the pain of not knowing why their child died and may help to inform on decisions about trying for a family again. The next step now is for genome sequencing testing to be offered on a national scale.
Professor David Rowitch
Chief Scientific Officer of NHS England, Professor Dame Sue Hill DBE, who is responsible for the development of genomics across the NHS said: This Cambridge trial is important because not only does it show the potential benefits of whole genome sequencing to significantly improve care for seriously ill children, but it also demonstrates this technology can be delivered as part of a mainstream NHS service.”This project was supported by funds from by the National Institute of Health Research (NIHR), the Cambridge Biomedical Research Centre, the Rosetrees Trust and Isaac Newton Trust and was featured on the BBC.
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