Australian Institute for Bioengineering and Nanotechnology (AIBN) Senior Research Fellow Dr Mohammed Shaker and Phenomics Australia Scientific Director Professor Ernst Wolvetang, head of the In vitro Genome Engineering and Disease Modelling Service and organoid expert, worked with a team to develop a synthetic organoid that mirrors the brain of a person with Down syndrome, to explore why people born with the genetic condition are more vulnerable to the coronavirus.
A first of its kind brain organoid grown at The University of Queensland has helped researchers identify therapies that reduce the impact of COVID-19 on people with Down syndrome.
“The risk of hospitalisation and death from coronavirus is much higher for people with Down syndrome, but until now there has been no clear data that explains why,” Dr Shaker said.
“Thankfully, our lab-grown organoids allow us to unlock this information and find ways to address the problem.”
Organoids are tiny, synthetic organ replicas grown from human stem cells that researchers use to carry out experiments that would be ethically and practically difficult in live subjects.
The team grew Down syndrome brain models and encased them in a layer of specialised cells known as the choroid plexus, effectively creating an organoid with two functional brain domains for the first time.
Testing on the new organoid models revealed that certain components of the choroid plexus are underdeveloped in people born with Down syndrome.
“The barrier function of the choroid plexus prevents coronavirus from infecting brain cells, and this barrier is compromised in people with Down syndrome,” Professor Wolvetang said.
“It means a crucial line of defence is missing and explains why patients in this cohort experience more severe COVID-19 symptoms.”
The lab used the organoids to screen drug therapies that could compensate for this vulnerability, including the US Food and Drug Administration approved drugs Avoralstat, Camostat, Nafamostat, and Remdesivir.
Dr Shaker said it was clear that human brain organoid models could be important medical tools that offer unprecedented insights and potential drug screening for a range of conditions beyond Down syndrome and COVID-19.
“This work exemplifies how increasingly sophisticated human brain organoid models can be used to discover the cellular and molecular processes driving neurological diseases,” he said.
“It also shows that these organoids are crucial tools that allow us to evaluate the safety and efficacy of new therapeutics at scale.”
The research was published in the journal Science Advances.
Professor Wolvetang and Dr Shaker were assisted by AIBN colleagues Bahaa Al-mhanawi and Sean Morrison as well as Professor Alexander Khromykh, Dr Andrii Slonchak, and Julian Sng from the UQ School of Chemistry and Molecular Biosciences, and Professor Justin Cooper-White from the UQ School of Chemical Engineering.
This article first appeared at Australian Institute for Bioengineering and Nanotechnology
Phenomics Australia provides a national centre of expertise and service provision to deploy a more comprehensive and sophisticated range of in vitro Genome Engineering and Disease Modelling capabilities to understand the functional consequences of DNA sequence variation in the human genome for health and disease while maintaining the expertise for in vivo disease modelling and genome engineering. To meet the high demand for adaptable and scalable disease-modelling platforms for improved diagnosis, Precision Medicine for genetic disorders, and therapeutic development by both academia and the biopharmaceutical industry, Phenomics Australia offers In Vitro services through a collaborative consortium of ten laboratories and facilities across Australia, operating at ANU (ANU Centre for Therapeutic Discovery), Perkins (Translational Cancer Research Program in Oncology), Monash (Monash Organoid Program & Monash Genome Modification Platform), MCRI (iPSC derivation & Gene Editing Facility), Peter Mac (Victorian Centre for Functional Genomics), UMelb (Centre for Stem Cell Systems & Stem Cell Disease Modelling Laboratory), UQ (In vitro Genome Engineering and Disease Modelling Service), and VCCRI (Stem Cell Production Facility iPSC Reprogramming Service)
