Watch Dr Leon Larcher accept the research grant award and hear a bit about the project.
Project Summary:
Every day in Australia, two people are diagnosed, and two die from motor neuron disease (MND). MND is caused by the loss of special cells (motor neurons) in the brain and spinal cord that control movement, eventually leading to paralysis and death. MND patients seldom survive beyond five years from diagnosis and treatment options are limited, with no new treatments becoming available in Australia in the last 30 years.
A variation in the C9ORF72 gene is a common cause of an inherited form of MND. To overcome the effects of this genetic change, we have developed a compound that can bypass the disease-causing mechanism. However, before our compound can be tested in patients, we must demonstrate that it is safe and effective. MND is a variable and complex disease, influenced by genetics and lifestyle factors that can subtly impact how patients respond to treatment. It is therefore essential that we consider this variation when testing new treatments. Recent advances have allowed us to use skin cells donated by patients and grow 3D “brain-cells-in-a-dish” or organoids, that can better represent patients’ genetics and mimic the structure, function, and interactions within the human brain and spinal cord.
In this study we will grow brain and spinal cord organoids using cells donated by MND-patients and utilise these 3D models to test our new drug candidate as a potential treatment for C9ORF72-linked MND/ALS. We will also use these models to better understand the disease and develop a platform for future drug testing.
Outcomes:
This work shows that spinal cord organoids grown from patient cells can effectively reproduce key features of C9ORF72-related MND in the laboratory, giving us a viable platform to test new therapies in a human-relevant system. By combining these organoids with single-cell RNA sequencing, we can now examine how individual cell types respond to treatment at a level of detail that was not previously possible.
For people living with MND, these findings are an important step towards more personalised treatments. In the future, brain and spinal cord organoids grown from a patient’s own cells could help predict which treatments will work best for that individual, paving the way for safer and more effective clinical trials.
We thank the Brain Foundation and its donors for supporting this research and helping us take the next steps towards more personalised treatments for people living with C9ORF72-related MND.
You can learn more about these research results in the Final Report, linked below.
The Brain Foundation is dedicated to funding the next generation of Australian research into brain disorders, diseases, and injuries, with the ultimate goal of advancing diagnoses, treatments, and patient outcomes.