Case studies

Motor neurone disease (MND) results in the selective death of upper and lower motor neurons in the motor cortex and spinal cord. MND patients develop progressive muscle weakness that eventually leads to death within 3-5 years following diagnosis and there are currently no effective treatments.

Mutations in the SOD1 gene are the second leading known cause of MND. These mutations subsequently lead to unstabilised formation of the SOD1 protein increasing the likelihood of it misfolding. SOD1 mouse models develop a progressive motor neuron disease that is highly similar to the human disease and provide a valuable insight into the basic biology of MND. Due to their ability to recapitulate the disease pathology of MND, SOD1 mouse models are commonly utilised to assess the preclinical efficacy of therapeutics in order for the safe transition into human clinical trials.

Ultimately, our current research at the UOW animal facility aims to guide the future design and testing of drugs that target SOD1 stabilisation to create effective treatment options for people diagnosed with MND.

Research findings

Graft-versus-host disease (GVHD) is an inflammatory disorder and major complication following donor stem cell transplantation in people with blood cancers and other blood disorders such as bone marrow failure. Use of donor stem cell transplantation is a curative therapy for blood cancers, as the donor immune cells can mediate a graft-versus-leukaemia (GVL) effect to combat any residual cancer in the patient. However, these donor immune cells (graft) can also mount an immune response attacking other tissues (liver, gut, skin and lung) in the recipient (host) leading to graft-versus-host disease (GVHD).

GVHD occurs up to 50% of patients following a donor stem cell transplant and can be fatal in up to 30%. Current therapies use broad range immunosuppression, leading to increased risk of cancer relapse and infection, therefore better therapies are required to treat GVHD.

We use preclinical mouse models that mimic the GVHD and GVL responses and allow us to test therapies to assess disease outcomes. These models are termed humanised mouse models, in which immunodeficient mice (no immune system) are engrafted with human immune cells and/or human leukaemia cells.

These preclinical humanised mouse models of GVHD and GVL developed in the Animal Facility at UOW allow us to examine the role of different human immune subsets, their engraftment and their role in tissue damage and anti-leukaemia immune responses. Furthermore, this allows us to test therapies to examine how to improve GVHD outcomes, while retaining the GVL effect.

These preclinical models allow us to further understand GVHD and potentially translate findings to improve the quality of life and outcomes for people with blood cancer and other blood disorders.

Research findings

Rat in a holding box, poking its head out of a tissue box
Researcher in lab using the Animal Cat Scan device