Alexander disease (AxD) is a progressive, neurological disorder with marked disruptions to central nervous system function. AxD is caused by mutations in the gene for the Glial fibrillary acidic protein (GFAP), which forms crucial support in brain cells called astrocytes and is vital to many cellular processes. In AxD, high levels of cellular stress in astrocytes are seen and reflected in mitochondria. Understanding this interplay will uncover more effective therapies.
Impact
Until now, treatment for AxD has been both ineffective and inaccessible. Working with clinicians and donated cells from patients, we’ve modelled AxD in brain organoids. Studying AxD in 3D brain organoids can provide safer testing for potential interventions. This collaboration brings discoveries in the lab closer to effective and potent therapies in the clinic for neurological disease.
reNEW research
Our team uses innovative stem-cell techniques to make new brain organoid models of disease. With stem cells donated by patients, we’ve been able to model AxD in brain organoids with the same genetic background as the donor. This allows us to zero in on the functions and processes at play between GFAP mutations and severity of disease. Looking ahead, our research will pave the way towards effective therapeutic strategies for AxD and other progressive neurological disorders.
Image description
Shown here is a high magnification slice of a brain-organoid model of AxD. In purple are cell nuclei, in yellow, fibre-like threads wrapped around nuclei show astrocytes (with a GFAP mutation), and in pink are the energy-producing mitochondria.
Credits
Anna Leichter, Research Assistant, Dr. Kellie Veen, Research Officer, Velasco Lab, reNEW Melbourne.
