At present there is no diagnostic test for MND, and diagnosis is usually determined through clinical observations and by excluding other diseases. Because of this, a definitive diagnosis of MND can take up to several months.
By developing an effective diagnostic test for MND, we will be able to diagnose MND earlier and put in place effective care and support needs sooner. Another benefit to earlier diagnosis would mean that people living with MND can be started on riluzole much earlier.
Prof Richard Ribchester, and colleagues, at the University of Edinburgh have recently been awarded funding from the MND Association to develop a new technique that allows them to view the connections between the motor neurones and muscles, by inserting a tiny, powerful microscope. Former colleague Dr Samantha Price explains more:
MND can be incredibly difficult to diagnose and diagnosis often includes a clinical examination, blood tests, nerve conduction tests and magnetic resonance imaging (MRI). Another investigation includes assessing the health of the motor neurones, and the connections they make with the muscle (known as the neuromuscular junction).
This is currently investigated by an electromyography (EMG) or muscle biopsy, which can be highly invasive and painful procedures.
Prof Ribchester’s Association-funded research will use an entirely different approach to assess the health of these neuromuscular junctions.
The power of an endomicroscope
Using an incredibly powerful microscope, known as a confocal endomicroscope, the researchers will place a small probe (1.5mm in diameter) onto the surface of the muscle, which will allow the researchers to make live observations at the neuromuscular junction in the clinic.
Prof Ribchester said: “We are very excited by the future prospects for using our ‘microendoscope’ to look at the neuromuscular junctions inside a patient’s muscles. This will allow us to observe how the disease may be progressing or, more importantly, to assess the effect of novel and experimental treatments on the neuromuscular junctions in MND.
“In order to view the neuromuscular junctions properly, we need highly specific fluorescent dyes that will stick to the nerve endings and make them glow. This will enable us to ‘see’ the neuromuscular junctions clearly by the optical fibres in our microendoscope.”
By using fluorescent ‘glowing’ dyes, which bind to the nerve endings, this will enable the researchers to view the neuromuscular junction bright and clear. However, identifying these specific dyes will be the main focus of the project.
Prof Ribchester said: “We have already shown that our microendoscope works well in mice genetically-engineered to express a fluorescent protein on their nerve endings; however humans do not express this fluorescent protein so we will need to create a safe injectable dye in order to view the neuromuscular junctions in humans using our microendoscope.
“Therefore the most important step in this project will be using sophisticated molecular biology techniques to discover fluorescent dyes that can be used with our microendoscope, before testing them on human muscle tissue. This will enable us to identify the best dyes for viewing living neuromuscular junctions in patients.”
The importance of this research
Already tested in mice, the researchers aim to further develop microscopic clinical imaging by creating a fluorescent dye that can be used with the microendoscope in humans.
Ultimately, this technique will not only allow us to view live neuromuscular junctions in people, but it will be a step closer towards a diagnostic test in the clinic to enable earlier diagnosis and monitoring of new treatments.
Dr Emma Hodson-Tole’s MND Association-funded research at Manchester Metropolitan University (MMU) is investigating a pain-free diagnostic test for MND using ultra-sound technology – you can click here to view a video of Dr Hodson-Tole explaining her research.