$250,000 awarded by ALS Canada in partnership with La Fondation Vincent Bourque to Dr. Silvia Pozzi at the CERVO Brain Research Centre, Université Laval.
In recent years, scientists have observed higher levels of a specific protein, called Peptidyl-Prolyl Isomerase A (PPIA), in the fluid that surrounds the brain and spinal cord in ALS mice. This has also been observed in people living with the sporadic form of the disease (i.e. those who have no family history).
PPIA is a protein that is typically found inside cells where it completes its normal function, however, when the protein is released into the fluid outside of cells (in this case referred to as extracellular PPIA or ePPIA) there can be a negative effect. Outside of cells, ePPIA can bind to another protein, called EMMPRIN, and this interaction is thought to activate a biological pathway that eventually contributes to motor neuron death.
With this award, Dr. Silvia Pozzi will explore a new therapeutic strategy for ALS that targets this toxic protein interaction. In this study, Dr. Pozzi will further explore the effects of the interaction between ePPIA and EMMPRIN on motor neurons as well as other support cells in the brain, such as glia cells, which are thought to also play a role in the onset and progression of ALS.
In order to block the interaction between ePPIA and EMMPRIN, Dr. Pozzi will develop an antibody that specifically targets EMMPRIN. Antibodies are proteins produced by the immune system to protect the body against foreign invaders like bacteria and viruses, and work by binding to specific proteins on harmful agents and triggering their removal and/or destruction.
By designing an antibody specific for EMMPRIN, Dr. Pozzi hopes to prevent the protein interaction thought to lead to motor neuron death. The ability of the antibody to reduce inflammation and motor neuron death will then be assessed in various ALS mouse models. If the antibody proves to be successful at preventing motor neuron death in mice, the next step will be to determine if similar effects can be seen in humans.
Dr. Pozzi hopes to use this project as a start to a career based on developing antibody-based treatments in the lab that can be elevated to human clinical trials and strengthen Canada’s leadership towards a future without ALS.