Motor Neuron Disease (MND) is characterised by the progressive loss of motor neurons. Despite years of research into the disease, effective treatments remain extremely limited and half of patients pass away within two years of diagnosis.
To date there is no cure for MND and only a few therapies exist that neither reverse nor stop disease progression but merely slow it. For example, riluzole, one of the most widely used MND therapies, extends survival by only a few months for many patients. This reflects a broader challenge across neuroscience research, where treatments that appear promising in laboratory studies frequently fail in clinical trials.
Since its first description in 1869, significant progress has been made in our understanding of genetic and biological mechanisms of MND. However, turning this knowledge into effective treatments is still proving difficult.
High rates of failure in clinical trials can be a result of a huge diversity of disease between individuals as well as the fact that lab models fail to capture and mimic this complexity of the human brain and spinal cord and the disease. These challenges highlight the need for multidisciplinary approaches, greater investment and out-of-the-box solutions along the research pipeline to successfully translate discoveries into therapies.
Better models for better treatment development
To develop better treatments, we need models that more closely reflect what happens in humans. Many of the models currently used to study MND fall into three main groups: animal models, labgrown cells, and computer models. While each has strengths, all come with important limitations.
Animal models, such as worms, flies, fish, and mice, help scientists study the disease in living organisms. However, these animals do not develop MND in the same way humans do, which means findings often do not translate well to patients. This is one reason why many treatments that look promising in the lab later fail in clinical trials.
Lab-based models, where cells are grown in dishes, make it easier to test drugs directly. However, these systems are much simpler than real human tissue and cannot fully reproduce the complex interactions between different cell types that drive disease progression.
Newer approaches using human stem cells allow scientists to generate patient-derived nerve cells in the lab. These models are more relevant to patients and can better reflect how the disease develops in people. Human stem cell systems are increasingly being viewed as an important route towards building more predictive, scalable, and clinically relevant models for neurodegenerative disease research.
The ‘stars’ of motor neuron disease
For decades, MND research has focused predominantly on motor neurons themselves. However, growing evidence suggests that other cell types within the brain and spinal cord may also play a critical role in driving disease progression. Among these are astrocytes, named after the Greek words for “star” and “cell” because of their distinctive shape, which are the most abundant cell subtype in the central nervous system (feature image).
Despite the label of being ‘helper’ cells, more recent research shows that they are anything but passive bystanders. Astrocytes are involved in almost every aspect of nerve cell functions, and they maintain their environment and regulate chemical signals between neurons and their energy use. Because of these broad responsibilities, dysfunction in astrocytes can have major consequences for the nervous system.
In MND, astrocytes appear to lose their protective functions and instead contribute to neuronal damage by adopting inflammatory and toxic states. Researchers still do not fully understand whether these changes are a cause or consequence of disease progression, creating an ongoing “chicken-and-egg” debate within the field. However, increasing attention is being directed towards astrocytes as potential drivers of neurodegeneration rather than passive bystanders.
The appearance of astrocytes in research papers has only picked up in the last 20 years and is still not comparable to the spotlight that neurons receive in this space. Scientists are still working to understand the diversity of astrocyte subtypes, how these cells change throughout disease progression, and whether they could serve as effective therapeutic targets. This emerging shift in focus has opened new opportunities to rethink how MND is modelled and studied.
Building human-relevant astrocyte models
My research focuses on developing human-relevant disease models that better capture the role of astrocytes in MND. By combining genetic studies of brain tissue from people who had MND, with cutting-edge lab models generated from human stem cells, this approach will allow better identification and confirmation of specific ways astrocytes contribute to the disease. The ultimate goal is to create disease models that closely mimic real-life conditions, allowing researchers to test potential treatments aimed at restoring normal astrocyte function.
These models could also improve how new therapies for neurodegenerative diseases are developed. By recreating key disease-associated cellular interactions in the laboratory, researchers may be able to identify new treatment targets in systems that more accurately reflect patient biology, improving confidence that findings will translate into clinical benefit.
Improved disease models may also help address one of the central challenges in neurodegenerative drug development: the high failure rate of clinical trials. Systems that better reflect human disease biology could enable earlier identification of ineffective therapies while accelerating the progression of more promising candidates into clinical testing.
Collaboration at the interface of academia and translation
This project is being carried out through an Industrial Fellowship supported by the Royal Commission for the Exhibition of 1851, a long‑standing organisation established to advance science and innovation by supporting early‑career researchers working at the interface of academia and industry. The research brings together the Sheffield Institute for Translational Neuroscience (SITraN), a world‑leading centre focused on understanding and treating neurological diseases such as MND, and LifeArc, a medical research charity dedicated to turning scientific discoveries into life‑changing treatments for patients.
By combining patient‑focused neuroscience research with industrial expertise in drug discovery and translation, this collaboration aims to bridge the gap between understanding disease biology and delivering practical treatments. The project represents an important step forward for people living with MND, offering hope for meaningful progress against this devastating condition.
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