DOCUMENT

Headlines 9 Before a successful project is funded, we require evidence of approval by a New Zealand ethics committee. Animal ethics committees operate under a Code of Ethical Conduct approved by the Ministry for Primary Industries (MPI), which includes representatives from organisations such as the SPCA and the NZ Veterinary Association. The committees are guided by the principles of reducing, refining, and (wherever possible) replacing the use of animals in research. She’d been investigating whether it was possible to grow a type of brain cell, known as an astrocyte, from newborn mice in a petri dish. Although the cells had normal astrocyte function, they’d been engineered to be bright green for easy handling. She then wondered whether she could genetically engineer these astrocytes into cancer cells. If that was possible, then the bright-green cancerous astrocytes could be put back into the same strain of mouse. There’d be no tissue rejection because the astrocytes would be immunologically identical to the host. It was a sound prospect, but it meant she had to work out how to turn these astrocytes into cancer cells. For that, she turned to international work that had been done over the last two decades. This involved wide-scale sequencing of the DNA material found in tumours, including the sequencing of glioblastomas. Dr McConnell decided to use the common mutations found in different subtypes of human glioblastoma and engineer them in the brains of mice to see if they led to glioblastoma. Dr McConnell was surprised and excited to see they did. “It was the first time ever that I had a project that worked exactly as I hoped it would.” Using these models enables researchers to develop and test drugs for their potential in glioblastoma in just months, something that would take years in clinical trials. “Basically, it can save a lot of time,” Dr McConnell explains. “We know that trials give patients hope, but I believe running a trial that proves to be futile isn’t helpful to either the patient or the bigger research picture.” These models should be able to quickly single out the best candidates for drug development and test how they work, saving precious clinical trial resources for drugs that have true potential. The model can now be used to test immunotherapy too. This is the activation of a patient’s own immune system to eliminate the tumour. It’s been an appealing option for some time, but with current mouse models not having an intact immune system, it’s been impossible to test until now. Dr McConnell says there are plenty of researchers keen to use the model in New Zealand, but she wants it used as widely as possible to speed up glioblastoma research worldwide. The work is still ongoing, but Dr McConnell and Devlin Forsythe will share their findings at conferences later this year in Europe and the United States. The Neurological Foundation funded a small project grant to establish whether mutations formed tumour cells in mice. After proof they did, another project grant for $185,233 (both generously supported by Merrill Holdsworth) was awarded for Dr McConnell’s glioblastoma work in 2022. “We know that trials give patients hope, but I believe running a trial that proves to be futile isn’t helpful to either the patient or the bigger research picture.” Dr Melanie McConnell Engineered astrocyte cells transplanted into the brain of healthy mice form glioblastoma-like cancers. This section shows the mouse brain cancer invading the normal surrounding tissue.