Developing a protocol to isolate motor neurons from post-mortem brains for molecular profiling

Summary

Motor Neuron Disease, also known as Amyotrophic Lateral Sclerosis (ALS), is a fatal neurodegenerative disease. Through the gradual loss of motor neurons, ALS leads to progressive muscle paralysis, with an average survival time of 2 to 5 years after diagnosis.

Unlike some medical conditions, there isn’t a definitive test for diagnosing ALS. This makes it difficult to exclude disorders with similar symptoms and can be incredibly frustrating for patients and their families who wait, on average, a year for a diagnosis. This research will improve the patient journey by informing an accurate DNA test to speed up diagnosis.

What are we doing?

To detect the early onset of the disease we have identified cell-type specific molecular signatures in the DNA that enables us to identify neurons from other brain cell type. We would like to refine our signatures to enable the identification of different neurons such as motor neurons which are specialised neurons that tell our muscles what to do. Once we have these unique signatures we will include them in our neurodegenerative blood test to identify dying cells using these unique molecular signatures. We hope that this test will help healthcare professionals to better diagnose neurodegenerative conditions and tell different neurodegenerative diseases apart.

How are we doing it?

We will conduct a series of laboratory procedures to extract and examine the DNA found in motor neurons. Using a method known as Fluorescence-Activated Nuclei Sorting (FANS), motor neurons can be isolated from brain tissues. FANS is a technique that tags cells with a fluorescent dye. A machine then groups coloured cells, helping researchers to isolate the motor neurons. Once the neurons are isolated, advanced technologies help to analyse their DNA, with a specific focus on their chemical makeup. We hope to identify specific modifications to the DNA (DNA methylation) that are unique to motor neurons. This refined approach can be used in the form of a DNA blood test to detect ALS neurons in the body.

What happens next?

At the end of the project, we will publish our groundbreaking approach for identifying motor neurons and their unique DNA characteristics. This will hopefully secure more funding and improve DNA testing for diagnosing neurodegenerative diseases.