The Masonic Charitable Foundation provides grant support to the Motor Neurone Disease Association’s MND research programme. The Association is funding a Masonic Charitable Foundation PhD Studentship at University College London. Now in the third year of his PhD, Sam Bryce-Smith is investigating the impact of faulty TDP-43 and FUS proteins in the development of Motor Neurone Disease. As part of this update, we also asked Luci Jago, Head of Trusts at the MNDA, to explain more about their work, which the MCF is proud to support. 

The Motor Neurone Disease (MND) Association is a global leader in funding and promoting pioneering MND research. With over 30 years of experience in identifying and funding the most promising research into MND, the Association has, and continues to play, a central role in supporting researchers in the MND field. Currently, there is no cure or effective treatment to stop the disease. The amount of MND research has increased over recent years, and this has helped to build a greater understanding of the biology behind the disease. This increased knowledge is vital for identifying and developing potential therapies.

The MND Association remains right at the heart of this, continuing to fund and drive research projects which push toward a world free from MND while also focusing on improving the lives of those with MND right now. As of 31^st December 2021, the Association is funding a total of 83 research projects which involve the work of around 177 committed researchers and support staff.

The Association’s current research strategy comprises four key areas that cover all aspects of MND – from ‘laboratory bench to bedside’. There are projects which try to identify the causes of MND and develop functional models to study the disease, while others aim to find unique biomarkers in people with MND to help speed up diagnosis and track the progression of the disease. Some projects also hope to turn the most promising compounds into drugs that are safe and will treat the disease, and others aim to improve the quality of life and care of people living with MND.

The Association is proud to offer project grants for both biomedical and healthcare research, as well as PhD studentships and Fellowships, which enable highly talented individuals to be trained in MND research and undertake projects. The PhD studentships aim to attract, train and retain talented science graduates who are just beginning their journey into MND research. The Association is currently funding 15 PhD studentship projects based at several different institutions throughout the UK, and 6 of these will begin this year.

As well as funding and supporting the work of researchers in the MND field, the MND Association organises an International Symposium to showcase and share new MND research. This event is the largest scientific and medical conference that is specific to MND in the world and creates an opportunity to bring the best and brightest scientists and clinicians together. The key to defeating MND lies in collaboration, and the symposium enables scientists, clinicians, healthcare professionals, and patient fellows from across the globe to share study outcomes, exchange knowledge and foster new collaborations that could enhance current research in the fight against MND. The 32nd International Symposium on ALS (amyotrophic lateral sclerosis)/MND, held virtually in December 2021, was attended by over 1500 people from 44 different countries, and planning is already underway for this year’s event.

The pace of research into MND has drastically increased over the last decade, and as a result of this, the number of clinical trials testing potential treatments for MND continues to grow. It is a hugely exciting time for the field of MND as many promising therapies are on the horizon, and knowledge of the biology that drives the disease is ever-increasing. Thanks to the dedication and collaboration of the MND community and our generous supporters, in partnership with MND researchers, scientists are moving closer to new treatments for the disease, and it is hoped that the current momentum of research can be maintained until MND becomes a treatable disease.

To find out more about the work of the Association and the research that they fund, please visit https://www.mndassociation.org/.

A huge thank you to the Masonic Charitable Foundation and London Freemasons for your generous support of our work; we couldn’t do it without you!

Sam’s Update

Luci has given a fantastic introduction to the disease and the work that the MNDA does in our search for treatments and cures, so I can dive straight into an update on my project!

I study the protein TDP-43, which has been found to be affected in the vast majority (> 95 %) of MND patients. In these patients, TDP-43 is lost from the nuclei of motor neurons and builds up elsewhere inside the cell, so it’s not where it is usually found and doing its job in healthy cells. TDP-43 is involved in producing RNAs, the ‘recipes’ our cells use as instructions to make proteins, which are the workers of our cells. I focus specifically on how TDP-43 affects where RNA recipes end. This can involve RNAs being cut short much earlier than usual, so the recipes do not contain the full instructions to make the protein. Other times, this just changes the end regions of RNAs. This doesn’t affect the instructions to make protein but can affect whether ‘postcode’ sequences are included, which deliver the RNAs to certain parts of the cell, so proteins can be produced where they are needed to do their jobs. This is especially important in motor neurons which can stretch up to 1m long!

In the past year, I’ve focused on identifying ends of RNAs that are absent or present at very low levels in healthy cells, but their levels increase when TDP-43 levels drop. To discover these events, we’ve taken advantage of RNA-sequencing data from cells in a dish where we have experimentally reduced the levels of TDP-43, so we can try to mimic what happens in MND. We were able to identify 94 of these events using data generated by our own lab combined with publicly available data from other labs across the world. To focus on events that are most likely to be relevant to disease and not just artefacts of using cells we can grow in a lab, we turned to sequencing data from deceased MND patients who had generously agreed to donate their tissue for research. We’ve found an extended end in a gene called ELK1, which shows a dramatic change when TDP-43 levels are lost in cells in a dish and also appears to be specifically increased in MND patients who have affected TDP-43. We are currently planning experiments to try and understand where this extended end is going in cells and how this change could be contributing to MND.

This article is part of the Arena Magazine, Issue 50 December 2022 edition.
Arena Magazine is the official magazine of the London Freemasons - Metropolitan Grand Lodge and Metropolitan Grand Chapter of London.

Read more articles in the Arena Issue 50 here.