Progress report from the research team
Principal Investigator, Prof Alan Mackay-Sim, provided the following update:
Non-SPG4 HSP investigation
Fan is continuing to work on specifying the similarities and differences between nasal stem cells from HSPers with spastin (SPG4) mutations and those with non-spastin mutations, using the automated microscope and automated image analysis. Data analysis indicates the cellular pathology of HSP is different in some ways in people with and without spastin mutations, but the challenge is to find how they are similar and whether drugs active with the spastin mutation will also be effective with non-spastin mutations. The work on peroxisome trafficking has been on hold because the live cell microscope has been out of action but has now been repaired.
In December, Professor Weiliang Zhu visited our institute. Professor Zhu is the director of the Drug Discovery and Design Centre at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Fan used the HSP stem cells and tested some potential drug candidates made by Professor Zhu. Fan and Professor Zhu are aiming to set up a formal collaboration for drug discovery for HSP. They intend to apply for grants from both Chinese and Australian sources.
We have now genetically engineered HSP cells from patients’ tissue samples to turn them into iPSCs (induced pluripotent stem cells) in the attempt to grow corticospinal neurons with HSP. These are the upper motor neurons that are primarily affected by HSP.
This involved infection with a virus that does the genetic engineering, followed by two months of cell culture that then eliminates the virus from the cultures. The work is about half way through that two-month elimination phase. The current focus is on planning the next steps of quality control that happens at the end of the 8 weeks, as the challenge of growing uniform and stable iPSCs that are both suitable and reliable for experimentation is a major one.
Mouse project and forward planning
The HSP mouse colony has been breeding while in quarantine, from which they will soon be released and that project can then really get underway. Forward planning towards funding and regulatory considerations associated with the application for early stage human clinical trials is taking place.