Project cost: £5,600

Motor Neurone Disease (MND) affects approximately 5000 people in the UK and involves the death of motor neurons that control the muscles in the body. Without the neurons supplying energy and key chemicals, the muscle starts to die, until the patient is left paralysed and eventually dies too, usually 2-3 years after the first symptoms appear. It is known that MND patients have defects in the key cellular components that make energy and this is observed not only in motor neurons but in the muscle cells and peripheral cells such as skin cells. Without sufficient energy generation, cells cannot perform key processes and will die. It is unclear at this point exactly how MND affects energy generation from different fuels (e.g. sugars, fats, proteins, amino acids) in patients and which are the exact fuels affected.

Seahorse

Skin cells are an easily accessible source of patient material and furthermore, have the potential to become a diagnostic tool in MND, using the cells as a way to discover biomarkers of disease, which potentially may help diagnose patients faster. The aim in this study is to use patient skill cells to build a metabolic profile of MND patients and look for similar profiles between patients that are different to controls. To carry out the work, the study will use a recently established metabolic screening technology (Seahorse – previously funded by Neurocare) which allows simultaneous analysis of over 80 different cellular fuels to assess exactly where the defects lie in MND patient skin cells.

If the pilot study is successful, researchers will be able to show MND specific metabolic profiles. They will then be able to seek further funding to test all their patient skin-cell cell lines and develop a MND specific metabolic dysfunction signature that could be used to diagnose patients. The researchers will also be able to use the technology to metabolically profile MND patient motor neurons that have been grown from their skin cells using stem cell technology recently developed at the Sheffield Institure for Translational Neuroscience (SITraN). This will allow them to assess how MND affects energy generation in motor neurons and how it compares to skin cells. If the researchers can pinpoint which fuels are affected then can even develop a specific nutritional supplement to give to patients to help the neurons cope with the disease.