Progress report from the research team
This year has been productive so far in moving towards a clinical trial. Our immediate goal is to strengthen the “biological case” to take to the Therapeutic Goods Administration (TGA) for approval for a clinical trial. Before approval for a drug trial, the TGA requires evidence for how a drug candidate works (the “mechanism of action”) in target cells. So we are extending our experiments to show that our drug candidate, which works in HSP patient-derived olfactory stem cells, has similar actions in neurons (nerve cells).
In Carolyn Sue’s lab in Sydney, Gautam Wali and the team are making neurons from patient-derived “induced pluripotent stem cells” (iPS cells). These are like embryonic stem cells that are made by genetic engineering from patient’s skin cells. We are now well down this road. We have made the cells and are doing the important quality control experiments, to make sure we have got them right. iPS cell colonies are notoriously variable and it is essential for reliable results that quality control on the cells manufactured is precise. We have been optimising the method to make the iPS cells differentiate into neurons and have started this in iPS cells from an HSP patient with a SPAST mutation.
In Alan Mackay-Sim’s lab in Brisbane, Yongjun Fan has been further exploring how the biology of patient-derived olfactory stem cells from patients with and without SPAST (SPG4 HSP) mutations are the same or different. This will give us a better idea of the potential for a drug developed for cells with SPAST mutations to also work for cells with different HSP mutations.
Meanwhile Gautam submitted for publication the first manuscript that is part of his PhD project. This is a big step for him and we have our fingers crossed that it will move quickly through the review process. This new research paper has been submitted to a scientific journal and reports on studies into peroxisome trafficking and oxidative stress in HSP cells.