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Developing a mouse model and treatment for SORD neuropathy 

Dr James Sleigh and colleagues from University College London will use a mouse model of SORD neuropathy to test potential gene therapies for this condition.
Details
Principal Investigator
Dr James Sleigh
Institute
University College London (UCL)
Official title
Developing a mouse model and treatment for SORD neuropathy
Duration
Two years
Total cost
£148,960
Conditions
Charcot-Marie-Tooth disease (CMT)
Year
2024

Background

SORD neuropathy is a type of peripheral neuropathy (a condition that affects nerves outside of the brain and spinal cord, called peripheral nerves) in which the gene called SORD is changed. People living with SORD neuropathy experience progressive muscle weakness, loss of sensations in the body and difficulty walking. 

The SORD gene produces a protein called sorbitol dehydrogenase, which has an essential role in removing sorbitol (a sweet alcohol molecule that is often found in fruit) from cells. Sorbitol is toxic to cells such as motor neurons, but the reason for this toxicity is unknown. If SORD doesn’t work properly, people develop peripheral neuropathy and have high levels of sorbitol in their blood. 

The researchers led by Dr James Sleigh have recently created a mouse y that doesn’t have the SORD gene. This mouse can be used as a ‘model’ for SORD neuropathy – sorbitol accumulates in motor neurons of these mice, which results in muscle weakness, just like in people living with SORD neuropathy. The mice will be used to identify the most important features of this condition. The team will also develop and test a gene therapy that will prevent the build-up of sorbitol in motor neurons, treating SORD neuropathy. 

What are the aims of the project?

As part of this project, the researchers aim to: 

  1. Understand the impact of sorbitol accumulation on the peripheral nerves of the mouse model of SORD neuropathy. 
  2. Create and test a gene therapy that reduces the build-up of sorbitol in motor neurons. 
  3. Identify and track key biomarkers in the blood of SORD neuropathy patients and compare them with their symptoms.  

The importance of this study

Mice that carry the same genetic changes as people living with muscle wasting conditions help us understand lots about the condition. They also provide a safe and relatively quick way to test potential therapies and treatments. Should Dr Sleigh’s research team identify the biomarkers of SORD neuropathy, this study could have a strong impact on monitoring the progression of this condition as well as the design of future therapies.  

Biomarkers

Biomarkers are molecules, proteins or other naturally occurring substances that are found in blood or other bodily fluids. The presence, or absence, of them can be a sign of the progression of a condition. Biomarkers can also be measured during a clinical trial to see if a potential treatment is having an effect on the condition. 

We’ve already made great progress.

But there is still so much that needs to be done. Together, we can change the future of muscle wasting conditions. Join us. Today.