Refinement of therapeutic intervention in a mouse model of amyotrophic lateral sclerosis
Aim
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a neurological disease in which muscles waste away leading to loss of movement and basic functions like breathing, eventually resulting in death. There are approximately 5,000 sufferers in the UK and no known cure. Scientists can study mice in order to understand what is happening at the cellular and molecular level and new therapies are tested by how much they extend the lifespan of the mice. The mice experience substantial levels of suffering due to the progressive nature of the disease. The aim of the research is to refine this process to limit the suffering and potentially reduce the number of mice used in this research.
Method
A particular problem in treating ALS is to deliver therapeutic drugs to the motor neurons, which are buried deep within the spinal cord. The effects of drugs can be measured using fluorescent probes which are injected into the mice. This will enable direct measurements to be taken of how well the drug is working in motor neurons in the spinal cord of the mice. An obvious benefit of this is that the most effective drugs and the doses of them to use in experiments can be identified without having to let the mice develop paralysis.
Implications for the 3Rs
By studying the effects of drugs at an earlier stage, before the mice lose a substantial number of motor neurons and become paralysed, this research will refine the experiment and limit suffering. Equally important in terms of animal welfare, is the ability to exclude therapies that are ineffective at an early stage in the drug development process, thereby reducing the amount of animal testing carried out. On an estimate of 100 drugs being tested per year worldwide, the number of mice used would be reduced by 2,500.
