How close are we to a cure? From Jessica Lee, our Director of Research

My Name’5 Doddie Foundation and our search for a cure has been hitting the headlines recently, thanks to the huge efforts of Lewis Moody, his friends and family. Lewis and many others go the extra mile to raise funds to boost our research activities. So how close are we really to finding a cure?

I’d describe a cure as a treatment that completely stops and even reverses any symptoms caused by MND. This is likely to be a cocktail of treatments, specific to each person, combined with early diagnosis. Realistically, a cure is not around the corner just yet, but we are getting closer to effective treatments.

An effective treatment is one that would significantly slow down the progression of MND. There’s been a lot of progress in the past twenty years, and the scientific community generally hope and believe that effective treatments for MND are not too far away. However, there are still many challenges and unknowns ahead and we have much more to learn about this complex disease.

Research progress

The last twenty years have seen major advances in our understanding of MND and our approaches to treating it. For a brutal condition like MND which typically progresses very quickly, research progress can never be quick enough, and Doddie was always the first to challenge that. But incremental scientific progress has been happening, and the pace of research is only accelerating.

Two decades ago, MND was a mystery. Today, we understand the disease much better and have a pipeline of promising potential treatments that are currently being assessed in clinical trials.

So, what have the major discoveries been?

1. 2006: We discovered that the protein, TDP-43, is dysregulated in ~97% of people with MND. This finding provided the first unifying mechanism for the majority of the disease. There are now many efforts to target this protein with new treatments.
2. Early 2010s: An explosion in our understanding of the genetics underlying the disease enabled us to pinpoint many of the genes that cause familial MND (MND that runs in families) including C9orf72 and FUS.
3. Mid 2010s: Neurofilament Light Chain (NfL), a blood-based biomarker of motor neuron degeneration, became widely accepted as a good biomarker of MND progression. It is now tested in clinical trials to measure effectiveness of treatments and has become the basis of the regulatory decision for tofersen (more on tofersen soon…).
4. Late 2010s: Stem cell technology matured and became so accessible that cells in skin samples taken from people with MND could routinely be transformed into motor neurons in the laboratory and studied extensively. This step-change in technology has allowed our researchers to understand MND on a deeper level.
5. 2023: The first treatment to significantly slow disease progression, the genetic therapy tofersen, was approved by the FDA for treating SOD1-MND (which is caused by mutations in the SOD1 gene and accounts for around 2% of all MND cases) – a landmark moment demonstrating that when we understand the cause of MND, we can develop effective treatments.

Where are we today, and why am I optimistic about the future?

Due to our evolving understanding of MND, a groundswell of awareness and funding globally, we are officially now in a translational era of MND research. That means "translating" advances in our understanding of the disease into treatments.

We’re not only benefiting from progress in MND but also from advances in related fields, such as the development and evolution of genetic therapy approaches.

Tofersen came first. Soon, we should hear from the promising phase 3 trial of ulefnersen, a genetic therapy for FUS-MND. Next, comes a pipeline of treatment approaches targeting different aspects of biology in sporadic MND – the kind of MND that has no family history and, in many cases, no known genetic cause.

Some of these treatments target TDP-43 and other related genes. Others address key areas of MND biology, such as inflammation in the brain and nerves and problems with the cell’s energy supply. Many of these treatments are still in the early phases of clinical trials, but the field is following their progress with interest.

There’s also a strong movement in the research community to find more effective and faster ways to assess new treatments in clinical trials. For example, the UK’s EXPERTS-ALS is testing treatments in a new “pre-trial” platform to enable rapid assessment of efficacy before expensive and more time-consuming trials are undertaken.

The pace of research feels fast, collaborative and has real momentum behind it.

What are the challenges, and what can we do about it?

Although we do have a pipeline of potentially promising treatments, drug discovery and development remains challenging. Drugs can fail for many different reasons, such as unexpected safety issues or a drug not being able to engage its target like we’d expected.

It is critical that we continue to deepen our understanding of MND biology and develop new treatment approaches to boost the pipeline further. Doing this means we are taking more shots on goal and mitigating against the high failure rate of drug development.

That is exactly what we are doing at My Name’5 Doddie Foundation:

• We are funding international groups of researchers to uncover new aspects of MND biology and identify innovative treatment avenues.
• We are delivering the UK’s only annual grant scheme focused on developing new MND treatments, ensuring we are pumping innovation into the treatment pipeline year on year.
• We are supporting high risk, high reward research to open up completely new approaches that could transform the field, because we’re not here to play it safe.

What's next for us?

We have big ambitions. As Doddie said: MND is not incurable, it’s just underfunded.

Finding treatments for MND is not easy. A cure is not just around the corner, but we hope that effective treatments are not too far away. This is a long road, but we are getting there. We’re making progress and we need your help.

Together, let’s fund more cutting-edge science and accelerate progress towards effective treatments and, ultimately, a cure for MND.