In August 2020, the Whitrod family discovered their baby girl had a rare and progressive genetic disease called SPG56. They discovered how little doctors knew about this incurable disease and approached genetic researchers around the globe to begin finding a solution.
10 months later, the Whitrods had connected with internationally renowned researchers and experts in rare genetic diseases from research institutes at both the University of Queensland and Griffith University.
This expert team of scientists have developed a coherent and collaborative plan to find a treatment for this currently incurable condition and in June 2021, the Whitrod family kickstarted the funding for this project to launch.
The ultimate goal within this collaboration, is to meet the urgent need for drugs to treat sufferers of SPG56 with novel modes of action that can change the course of the illness, not simply treat symptoms.
As a coherent team, the two institutes use patient derived stem cells and study them in-vitro (in the dish) to understand how mutations in the SPG56 gene cause the disease. Since SPG56 is primarily a neurological disease, the cells under investigation should be nerve-like cells. The investigators will test thousands of existing chemicals (including approved drugs and/or other compounds) to see if the abnormalities in patients’ cells can be corrected.
At Griffith University, under the leadership of 2017 Australian of the Year, Emeritus Prof. Alan Mackay-Sim, the researchers are using olfactory stem cells from SPG56 patients. These are neural stem cells (ONS cells) that reflect very early formation and the development of the brain. Encouragingly, this research approach has been done with the more common spastic paraplegia- SPG4. The fact that Griffith is already heading into clinical trials in their SPG4 study, gives Our Moon’s Mission to find a treatment for SPG56 a very promising prospect.
Meanwhile at the University of Queensland, the team led by Prof. Ernst Wolvetang are generating patient-derived induced pluripotent stem cells that are then differentiated into neurons. The UQ team also develops “mini-brains” in the dish complete with multiple types of neurons and supporting cells, known as brain organoids. These lentil sized brains are used to further analyse the cellular basis of SPG56 as it would behave in Tallulah’s brain. Watch Prof Ernst’s fascinating TED talk on growing mini brains to solve big problems.
The synergy between these two groups allows a rapid and comprehensive program of drug discovery.
On a practical level, ONS cells are easily accessible (a biopsy through the nose) and cheap to grow and therefore suitable for high throughput screening of thousands of FDA approved drugs and/or compounds. iPSCs neurons and brain organoids are expensive to generate and grow and take a relatively long time to establish, though generate a more representative model of a human brain.
Therefore, the overall strategy is for Griffith University to do most of the fundamental studies establishing cell biology and screening in the ONS cells. We expect this will generate promising leads of compounds that can then be further investigated by the UQ team in the iPSC neurons and organoid. From that, the best compounds that appear to normalize the function in a realistic cellular environment can be identified.
Collectively over these phases, the Our Moon’s Mission team will develop a complementary and robust analysis of the disease throughout brain development, and the impact of potential treatments for SPG56 in vitro.
A moonshot for Our Moon’s Mission!
