LifeArc-funded documentary highlights pioneering scientific research into new targets for treatment of motor neuron disease

A new documentary has been released which follows a key discovery made by researchers at University College London that suggests a promising target for new treatments to tackle motor neuron disease (MND), a terminal condition.

Backed by LifeArc and other MND charities and the MND scientific community, the short-documentary ‘Turning the Tide’ details the scientific discovery. It shares first-hand the impact on the lives of people living with the disease and their hopes for ongoing research in the field.

It was funded as part of LifeArc’s MND Translational Fund to help accelerate promising treatments and innovations for patients.

MND affects nerve cells known as motor neurons in the brain and spinal cord that help tell your muscles what to do. These cells die and muscles start wasting away meaning people progressively lose the ability to walk, talk, eat and breathe. Currently, around half of those diagnosed die within two years and six people are diagnosed with MND every day in the UK with the condition currently affecting around 5,000 people.

The documentary highlights the team behind the research – Anna-Leigh Brown, Dr Oscar Wilkins, Dr Matthew Keuss and Professor Pietro Fratta – and their research at the University College London Queen Square Institute of Neurology. It identified how the loss of a protein (TDP-43) from the nucleus of motor neurons corrupts the genetic instructions required to make another key protein (UNC13A) that is vital for the normal functioning of the cells.

Lead author of the research, Anna-Leigh Brown, said, “We’ve known for over a decade that people who have variations in the UNC13A gene are at a greater risk of developing MND. By better understanding what goes wrong with UNC13A, we’ve opened the door to a whole range of possibilities. We hope that in the future, our work will lead to new treatments that slow down or stop disease progression and give valuable time for people living with MND.”

Their work brings together previous research to provide the evidence that loss of UNC13A function is one of the key things that goes wrong in motor neurons in MND. The research went a step further to identify how a type of treatment called antisense oligonucleotide technology, a form of gene therapy, could block this process and potentially slow down the progression of MND in most people diagnosed with it.

The potential treatment being tested is an emerging area of drug development that targets the cause of a disease at the genetic level, in this case, restoring the production of the UNC13A protein. This research is being backed by medical research charity, LifeArc, the Motor Neurone Disease Association (MND Association) and My Name’5 Doddie Foundation who have jointly awarded £500,000 to the UCL team.

Stéphane Maikovsky, Interim CEO of LifeArc, said: “This is a very moving film that captures how devastating MND is and highlights the significant unmet medical need given fewer than 10 per cent of people survive more than 5 years post-diagnosis. Funding pioneering research into the disease as part of our Motor Neuron Disease Translational Fund and Translational Challenge is critical to unlock desperately needed treatments for patients. This discovery marks a significant advancement in our understanding of MND and suggests an exciting target for future treatments.”

Professor Pietro Fratta, MRC senior clinical fellow and MNDA Lady Edith Wolfson fellow at the UCL Queen Square Institute of Neurology, said: “We now have the opportunity of switching this protein back on so that neurons that have gone silent can start functioning again. It will take time, but we aim to move our findings beyond the lab towards clinical trials and hopefully slow down or stop the progression of this devastating disease.”

Jo Knowlton, who is living with MND and features in the documentary, said: “I know I’d make a great wife and a great mother. I’m heartbroken that I don’t get to experience that. I keep expecting to wake up and for this nightmare to be over. I’d give anything for that. I can’t do anything for myself, I can’t scratch an itch or lift my iPhone. I want change, even if it doesn’t benefit me, if it benefits other people in the future that would make me really happy.”

Turning the Tide, produced by Mark Fielder and QuickFire Media and supported by LifeArc, MND Association, MND Scotland, My Name’5 Doddie Foundation, Mouse News Letter, Alan Davidson Foundation, UCL and The Francis Crick Institute is aiming to secure further funding to follow the progress of the team at UCL and highlight the process of getting a treatment from the lab through clinical trials to people living with MND.

The short-documentary is available to view here.