Summaries of 2024 research

What animals are you planning to use?

Rats and mice.

For what purpose are the animals going to be used?

“Ischaemia Reperfusion Injury” (IRI) is an inevitable consequence of kidney transplantation that leads to poorer outcomes in the short-term (delay in function or failure of transplant and increased rejection) and long-term (reduced longevity of the transplant and early transplant failure). Understanding IRI and finding treatments for it will improve outcomes in kidney transplant patients.

What will be the harms to those animals and how will these be limited?

The animals will undergo an operation to create the Ischaemia Reperfusion Injury to the kidneys, from which one of the adverse effects is postoperative pain. This may be of moderate severity and will be controlled with effective pain relief. The animals will be observed daily for clinical signs of any distress. One of the other risks is that the kidneys are damaged, and the animals may go on to develop kidney failure in the long-term. The animals will be humanely killed at 28 days, well before the potential development of chronic kidney failure.

What alternatives did you consider before embarking on the use of animals in your research?

We considered cell culture as a potential alternative. However, Ischaemia Reperfusion injury involves multiple complex biological processes and unknown interactions. To date there is not a suitable non-animal model and therefore the use of animals is the only current method available for the experimental assessment of these interactions.

What will be the expected benefits?

Identifying treatment strategies for kidney IRI will improve outcomes in kidney transplantation – both in the short and long-term. It will also potentially allow use of deceased organs that are currently discarded as they are deemed unsuitable for transplantation.

What animals are you planning to use?

Mice.

For what purpose are the animals going to be used?

To study the immune system during brain disease to understand what goes wrong with immune processes to identify new approaches to treating brain diseases.

What will be the harms to those animals and how will these be limited?

We use immune-deficient mice and limit harms by maintaining them in very clean environments, so they do not get infections. We use mouse models of brain disease and we limit harms by using only mild disease models to limit risk of harm.

We also administer substances to the mice, use mice with altered genes, and/or transplant cells with specific genetics. In the case of substance administration, there is possibility of toxicity, but using existing knowledge and careful dosing and monitoring to limit possible harms. Where gene-modified mice are used, the gene changes are not expected to cause harms to the animals.

In all cases, animals are appropriately monitored for unexpected harms with expert veterinarian advice when needed.

What alternatives did you consider before embarking on the use of animals in your research?

We use human cellular models to study diseases in a dish. This work is very active, both complementing and replacing the animal research.

What will be the expected benefits?

We expect to learn about the underlying mechanisms of specific brain diseases unlocking potential therapies.

What animals are you planning to use?

We will use mice and rats for our studies.

For what purpose are the animals going to be used?

We aim to understand how a part of the immune system called the “complement system” may cause damage in central nervous system (CNS) diseases such as Alzheimer’s disease, multiple sclerosis, and myasthenia gravis. This research will help us understand the roles of the complement system in CNS diseases and support the development of new treatments.

What will be the harms to those animals and how will these be limited?

Some animals may develop signs of disease, such as weakness or movement problems, signs of ageing, to help us study the disease progression. All work is carried out under strict Home Office regulations, and we follow detailed clinical scoring systems to monitor animal health and wellbeing.

What alternatives did you consider before embarking on the use of animals in your research?

We are using alternatives wherever possible, including computer models, cell cultures, and human tissue studies. These methods help reduce the number of animals used and focus only on the most essential experiments.

What will be the expected benefits?

Our work will improve understanding of how the complement system contributes to pathology in CNS diseases and help to develop better treatments for people living with these conditions.