To show our support for #GlobalMNDawareness day, Paul Wright, Principal Scientist, and Nick Darvill, Business Manager, explain the status of scientific understanding of MND and the ambition behind creating the joint fund with the MND Association to stimulate research into practical treatments.
Geoff Burrow, father of ex-Leeds Rhino player and MND sufferer, Rob Burrow, took part in the webinar for researchers interested in applying to the fund.
“It was great to have Geoff join the webinar and to know that he was interested to see what we are trying to do with the fund. Having a parent of a patient participate cuts through to why we are doing this call,” said Nick.
The brutal toll of MND
MND is a fatal, progressive, neurodegenerative condition. Messages from the motor neurones gradually stop reaching the muscles, leading the muscles to weaken stiffen and waste. It affects everyone differently and can also affect how some sufferers think and behave.
There is a 1 in 300 risk of getting MND across a lifetime in the UK, and it is most common between the age of 40 and mid 60s. Death from respiratory failure typically occurs within three to five years of symptom onset.
Disease progression for MND is not completely understood, particularly for sporadic cases. MND displays significant clinical and genetic heterogeneity and it is becoming clearer that the degeneration of motor neurones and progression of disease likely involves a cascade of sequential events.
There is only one drug currently licensed in the UK to treat MND – riluzole- but it has modest benefits and there are currently no disease-modifying, effective treatments for MND.
The disease progresses rapidly with affected people losing the ability to walk, talk, eat and ultimately to breathe. Half of those diagnosed die within the first year. Caring for MND patients puts a significant burden on families and carers.
Scientific advances in understanding
In the last two decades, research into MND has undergone an acceleration and this had led to exciting discoveries and improved understanding into the underlying disease mechanisms. There is now growing evidence that MND research is ‘primed’ for translation – taking that fundamental research into disease mechanisms and converting it into the development of interventions for MND.
Big leaps have been made: for example the discovery of more than 20 genes harbouring mutations that are the cause of some inherited forms of MND and the general consensus that the mislocalisation of a protein called TDP-43 is common to almost all types of MND. The science continues to move apace and neuroinflammation is an example of a process that has emerged in more recent years and is thought to play an important role in pathology.
MND treatments on the horizon
There are multiple treatments in the pipeline for MND that aim to target a variety of disease mechanisms. Drugs in development are seeking to prolong survival or to cure via a novel mechanism of action and many drugs in development for MND are also in development for other neurodegenerative conditions.
The pipeline includes small molecules, antibodies, cell therapies (mesenchymal stem cells and neural stem cells), and gene therapies including antisense oligonucleotides (ASO). Approaches in development are both novel therapeutics and repurposing of existing drugs.
One recent development was Amylyx’s AMX0035 which showed a slowing of symptoms in a Phase II/III study. The identification of the genetic basis for some inherited forms of MND has put MND at the forefront of developing antisense oligonucleotide (ASO) and gene therapy-based strategies for addressing neurodegenerative disease and there are multiple gene therapy strategies in early stage development for MND, with one being tested in a Phase II trial.
The therapy that has perhaps generated most excitement in the MND community in recent years is Biogen’s torfesen, which is currently in a Phase III trial and would be applicable as a treatment to the inherited form of MND caused by mutations in the SOD1 gene.
Another hotly anticipated therapy in development was BrainStorm’s NurOwn, a stem-cell therapy that was in Phase III trials, but recent results have shown that NurOwn did not meet the primary endpoint of slowing disease progression compared to placebo, although benefit was shown for a subgroup of patients. The failure of NurOwn highlights the difficulty in developing an effective treatment for MND, which continues to suffer from a high clinical trial failure rate.
In addition to better treatments, it well-voiced in the community that there is a need for better biomarkers for diagnosis, patient stratification and measurement of treatment efficacy as well as better clinical trial endpoints.
The LifeArc& MNDA translational research fund
The LifeArc & MND Association Translational Research Fund was launched in May 2021. It is a joint £1m fund designed to stimulate promising translational research and the development of therapeutic approaches that could feed into the pipeline of new treatments for MND patients as the search for better treatments remains a high priority for MND patients.
LifeArc hopes to be able to support a handful of high-quality research projects that have a genuine chance of progressing and eventually translating a therapeutic approach into an actual treatment that can be tested in clinical trials. Projects should have a clear delivery plan and outline a route to patients, but it is likely that funded projects will require further industry investment or grant funding to take a developed treatment through to clinical trials. Research funded by this call should help to de-risk a therapeutic approach and secure additional funding needed to take that next step.
The fund has just closed for applications, and the rigorous process of evaluating applications including external peer review and panel review will take place in the coming months. Funding decisions will be made in December by the panel.
Nick Darvill is a Business Manager at LifeArc. He is part of our Phil Fund team responsible for managing the Phil Fund portfolio as well as interactions and other funding schemes with other charity partners.
Paul Wright is a Principal Scientist at LifeArc. He is part of the Cellular Sciences team and leads a number of our Neuroscience projects.