One of our priorities has always been to ensure you know where the money donated or fundraised for The Nick Smith Foundation is spent – and the impact it has.
We made a substantial £50,000 donation to the Sheffield Institute for Translational Neuroscience (SITraN) earlier this year and it went towards a machine called a Nanostring Ncounter – a key piece of equipment helping the fight against Motor Neurone Disease.
We’re pleased to be able to say in its first few months of operation it is already having an impact:
- Over 200 samples have been interrogated using the machine looking at the levels of between 70 and 800 genes in each sample
- These are part of seven independent projects
- Three of these are MND-specific and the others are related to dementia and oncology, giving added value from the machine and enhancing learning across the centre
Dr Adrian Higginbottom, Senior Experimental Officer at SITraN, has written about its impact in detail:
The value obtained in the short time we have had, and been trained on, the Nanostring is clear; it has been used in 7 independent projects, 3 are motor neuron disease (MND) specific, 2 are dementia related and the other 2 were from the wider school and are related to oncology. Over 200 samples will have been interrogated, ranging between 70 and 800 gene targets, depending on the project being undertaken.
The Motor neuron specific projects were the driving reason behind sourcing the Nanostring in SITraN. The other projects have added value as we have not exceeded capacity, and will help with funding future maintenance of the machine.
Specifically, we are involved in 2 ongoing clinical studies for MND centred on understanding the benefits of low dose IL2, called IMODALS and MIROCALS. The reason is, evidence suggests inflammation has a role to play in MND, specifically a key role for regulatory T cells (Tregs) has been demonstrated, crucial in modulating normal neuroinflammatory responses. For MND patients, it has been shown Tregs are dramatically and progressively decreased in number with disease progression, suggesting immune responses will be sustained for longer in the central nervous system. Interleukin 2 (IL2) used at low dose has been shown to promote the selective increase in Tregs.
MIROCALS (http://www.mirocals.eu/en/) is a proof of concept phase II clinical trial, testing the validity of modulating Tregs using IL2 in MND and its safety. IMODALS is a pilot phase II clinical trial defining the activity and safety of a range a doses for subsequent use of the best dose in a phase II/III trial, again administering low dose IL2. The Nanostring has been pivotal in analysing the biosamples collected in these trials, studying the efficacy of the treatment, measuring the transcriptomic changes (gene signature) using the “Autoimmune Discovery” panel across treatment time. This off the shelf panel interrogates 755 genes simultaneously.
The major advantage is the time it would have taken to validate this many targets on this many samples in a conventional quantitative polymerase chain reaction (qPCR) type analysis is immense, months of wet bench work has been reduced to hours. Another advantage is the number of targets that can be investigated on a limited amount of our precious samples.
As yet none of the data generated on the Nanostring has been published, but several manuscripts are being drafted currently for submission in the near future.