At Understanding Animal Research, we make it our mission to keep you informed about developments in the world of animal research. To finish the year, here is a pick of the top ten stories of 2024 from our members that inspire and offer hope for the future.
1 . Gene therapy restores hearing in a toddler
Earlier this year, 18-month-old Opal Sandy successfully regained her hearing, becoming the first British person – and the youngest child in the world – to take part in a pioneering gene therapy trial that doctors say marks a new era in treating deafness. The toddler suffers from genetic auditory neuropathy. Her nerve impulses were unable to travel from the inner ear to the brain due to a faulty gene called OTOF. Opal’s treatment, which was part of the CHORD trial at the University of Cambridge, was based on a gene replacement therapy that was extensively validated in OTOF-deficient mice and tested for clinical safety and efficacy in mice and non-human primates (monkeys) in order to determine the optimal injection dose, volume, and administration route for clinical trials. Within four weeks of having the gene therapy infusion to her right ear, Opal responded to sound and at 24 weeks, she had close to normal hearing levels for soft sounds. A real success!
Gene therapy is currently considered the most promising strategy to cure genetic diseases such as inherited hearing loss. More than 40 studies have reported successful hearing restoration via gene therapy in animal models, with each focused on a deafness-causing mutation among 20 genes.
2. A new device to treat epilepsy
In a world first, a teenager who suffered from daily seizures was fitted with a deep brain stimulation (DBS) device in his skull as part of a UCL-sponsored clinical trial. The device reduced the boy’s daytime seizures by 80%.
This stimulation of the deep brain tissues was pioneered in animals. DBS had already been proven successful in treating childhood epilepsy, but the devices had previously been placed in the chest with wires running up to the brain. This was the first time the new configuration had been tested, hopefully reducing complications such as infection or device failure.
3. First new treatment for asthma attacks in 50 years
The monoclonal antibody benralizumab (sold under the name Fasenra) is already in use for severe asthma in emergency situations but a new study, led by King’s College London, suggests it could be used routinely, and be a game changer for people with asthma and COPD. Treatments for asthma and COPD have not changed in 50 years despite the diseases causing a combined 3.8 million deaths worldwide every year. People treated with the new therapy were less likely to be admitted to hospital, need another round of treatment, or die. The research team at King's College London said the drug is a "game-changer" that could "revolutionise" care.
The development of benralizumab involved animal research at different stages, and the monoclonal antibodies were themselves derived from mice that had been modified (or humanised) to prevent the antibodies from being rejected by the human body. Safety tests for human use were also assessed in monkeys. The antibodies were then produced for use as an asthma drug using Chinese Hamster Ovary (CHO) cells – a common technique to produce proteins.
4. New approach for treating schizophrenia – a first in 50 years
A new treatment for schizophrenia – backed by Wellcome-funded research – has been approved by the FDA – a first in 50 years. It has the potential to change the lives of millions of people living with the condition globally. The new drug, Cobenfy, performs much better than other treatments and with fewer side effects because of the way it reacts with brain cells. These effects were initially discovered using animal research. Animal studies using mice and rats showed that one of the drug’s ingredients, xanomeline, supported cognitive functions and could control the symptoms of schizophrenia.
5. An mRNA vaccine against cancer shows promise in humans
The mRNA-4359 immunotherapy vaccine is just one of many cancer vaccines entering clinical trials around the world. The therapy works by presenting common markers of tumours to patients’ immune systems, training them to recognise and fight cancer cells that express these markers, and potentially eliminate cells that could suppress the immune system. Results from the Phase I trial led by a team at King’s College London – also the first-in-human study of the therapy – designed to test the safety and tolerability of the immunotherapy, as well as the radiographic and immunological responses, show the immunotherapy creates an immune response against cancer in a way that could help to treat cancer more effectively and is well tolerated.
Although they should be treated with caution, these promising early results support further research into mRNA-4359. Preclinical testing in both cell and animal models of cancer provided initial evidence that mRNA-4359 had an effect on the immune system, providing a rationale for it to be offered in early-phase clinical trials.
6. Mapping out the pig
This year, researchers have gained huge new insights into pigs. First, a new study by the Babraham Institute and the Pirbright Institute provided an “atlas” of pig lung immunity, detailing how immune cells in pig lungs change after influenza infection or vaccination. This study has, for the first time, examined the active genes in pig lung cells to make a “map” of how the immune system functions following influenza infection or vaccination. Humans and pigs share a similar anatomy and physiology making pigs a useful model for understanding the immune system – among other physiological features – for both species.
This research comes after a study by the Pirbright Institute gained insights into the similarities between the immune systems of pigs, cows, mice, sheep, and humans. Researchers showed that an important section of our immune system involving the molecule MR1 and MAIT cells is evolutionarily conserved across multiple species. This new research could pave the way for innovative treatments and vaccines.
Finally, scientists at the Pirbright Institute have generated a nearly complete genome assembly for an inbred domestic pig breed, enhancing the animal’s potential use as a biomedical model for better human and animal health. In addition to the genome assembly, the researchers also developed a transcriptome atlas of the Babraham pig – a collection of data that provides information about gene expression patterns across different tissues within an organism.
7. Bacteria could trigger type 1 diabetes
For the first time, scientists from Cardiff University, have found that proteins from bacteria can trigger the immune system to attack insulin-producing cells, leading to the development of type-1 diabetes. In laboratory experiments, the researchers introduced bacterial proteins into cell lines from healthy donors and monitored the reaction of their killer T-cells – a type of white blood cell that’s involved in tackling bacterial infections. They found that strong interactions with the bacterial proteins triggered killer T-cells to turn on and attack cells that make insulin, causing type-1 diabetes.
Research had previously shown in mice a link between the part of the immune system triggered by pathogens and the development of auto-immune insulin-dependent diabetes.
8. New insight into improving immunotherapies
Immunotherapies aim to wake up the immune system so it can tackle cancer cells. Several immunotherapies are currently used to treat certain types of cancer, but right now, these treatments only seem to work in a minority of patients. By investigating in mice, the role of “natural killer cells”, and what happens to them when they enter the tumour environment, researchers at the University of Birmingham have developed a new understanding of how cancer interacts with our immune system, which could lead to improved immunotherapies.
Most currently used immunotherapies target a type of immune cell called a T-cell. Unfortunately, T-cells can only recognise certain types of cancer cells. But T-cells don’t work alone – they need help from other immune cells, notably NK cells, to be effective. Although NK cells tend to rapidly lose their anti-cancer functions once inside a tumour, the researchers found a way to give NK cells back their cancer-killing abilities in mice. A protein called Interleukin 15 (IL-15) is able to “wake up” the NK cells inside the tumours and re-enable their anti-cancer functions, allowing them to gain control over tumour growth.
9. New key to understanding Alzheimer’s disease
Researchers from the University of Liverpool have made a significant step forward in the understanding of Alzheimer’s disease. Using a mouse model, they have shed new light on how the disruption of mechanical signalling in the brain could lead to a condition which accounts for 60-80% of dementia cases worldwide.
The work in mice showed evidence that the Amyloid Precursor Protein (APP), known for its role in the formation of amyloid plaques in the brain, characteristic of Alzheimer’s disease, directly interacts with talin, a synaptic scaffold protein. For the first time, the researchers showed that the stability of the talin-APP relationship to one another is crucial for memory formation and maintenance. Misprocessing of APP observed in Alzheimer’s, disrupts mechanical signalling pathways, leading to synaptic degeneration and memory loss, thereby contributing to the progression of Alzheimer’s. Furthermore, if talin is removed then the processing of APP is dramatically altered. This is the first time this connection has been identified and could pave the way for therapeutic interventions.
10. Understanding the liver could lead to better cardiovascular treatments
A new discovery in mice about how the liver flushes cholesterol from the body could lead to more effective treatments for cardiovascular disease – the leading cause of death worldwide. By looking at transgenic mice, researchers from the University of Leeds found that bile production, which is vital for flushing excess cholesterol from the body, is affected by the rate at which blood flows into the liver via the “portal” vein that comes from the intestine. As blood flow varies throughout the day in response to movement, rest and food intake, it affects bile production. Bile production increases when blood flow decreases, which happens as a result of exercise or fasting. Conversely, it lowers when blood flow increases, which happens when people eat and rest.
The liver doesn’t have a constant and stable function but is able to sense changes and adjust its functionality depending on the body’s needs. Linking the liver, bile production, cholesterol and the cardiovascular system, this breakthrough provides an opportunity for the development of new treatments to tackle cardiovascular disease and prevent the progression of fatty liver disease. The findings could also help surgeons and experts better treat patients by better understanding the origins of their disease.
BONUS: Lemur communication shows how humans evolved to create music
A type of lemur called Indris, which communicates in rhythmic song, gave scientists at the University of Warwick an insight into how humans evolved to create music. The researchers found that the lemurs had consistent rhythmic patterns or beats in their communications, — much like music. Indris lemurs, along with humans, have the highest number of vocal rhythms in the animal kingdom, surpassing songbirds and other mammals. The findings highlight the evolutionary roots of musical rhythm, demonstrating that the foundational elements of human music can be traced back to early primate communication systems.
Our top three 3Rs stories:
Improving fish health and wellbeing in aquaculture
Lallemand Animal Nutrition and the University of Plymouth have announced a new initiative that aims to enhance fish resilience and welfare. The research will hopefully uncover the benefits of microbial solutions to the health of salmon in aquaculture. Researchers will investigate if the products can fortify and repopulate the epidermal and gill mucosal microbiomes after fish undergo ectoparasite treatments. The hope is that this will reduce opportunities for pathogen colonisation after disruptive events, and thus improve fish robustness and health. This could be a game-changer for fish farmers worldwide, improving animal welfare, and also global food security.
A new way to screen drugs reduces dependence on animals
Research fellow Dr Richard Naylor from the University of Manchester developed a new method – now used across the world – to easily and quickly screen new drugs for treating different kidney diseases using zebrafish larvae instead of mammals.
Until now, protein in the urine of mouse models or from human patients was mainly used as a marker of kidney dysfunction in disease and in response to drug treatments. Zebrafish models weren’t used because it was virtually impossible to test for protein in the urine of zebrafish larvae, due to the tiny amounts of urine produced which were immediately diluted in the fish tank. The researchers genetically modified zebrafish larvae to contain a luminescent molecule in their blood that leaks out of the kidneys when they are damaged and into the urine. This luminescent marker can then easily be detected in embryos using a luminometer. As such, it becomes possible to test the level of the marker in high numbers of larvae, not considered fully sentient by law at less than five days old.
With the new genetically altered larvae, the ability to use zebrafish to accurately monitor kidney dysfunction increases the appeal of pre-independent feeding stage zebrafish to model kidney disease for researchers worldwide. The model is a novel alternative to mammals which reduces the numbers of animals in research and drug screening, and enhances the care they receive. The research was awarded the University of Manchester’s 3Rs prize.
New recommendations for the adoption of NAMs in UK chemical regulations
NAMs – New Approach Methodologies – are modern methods of chemical testing that utilise advanced technologies to enhance the assessment and regulation of hazardous chemicals by improving the relevance, performance, speed and reliability of toxicological testing, and to support a transition away from animal testing.
A new report establishing recommendations for the adoption of NAMs in UK chemical regulation has been published by the Department for Environment, Food & Rural Affairs (DEFRA). As well as the suggestion that the UK could be a world leader in NAMs if these recommendations are followed, the report also argues that the strategic implementation of NAMs can significantly reduce, refine, and potentially replace the use of mammalian animals for chemical safety testing, while improving hazard assessment robustness and efficiency.
Last edited: 13 January 2025 15:09
