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
- CuATSM improves motor function and extends survival but is not tolerated at a high dose in SOD1G93A mice with a C57BL/6 background
- The PSX7 receptor antagonist JNJ-47965567 administered thrice weekly from disease onset does not alter progression of amyotrophic lateral sclerosis in SOD1G93A mice
- P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice