Eftekhar Eftekharpour and Soheila Karimi, University of Manitoba, Winnipeg, Canada

Targeting excessive lysosomal activity for prevention of cell death and enhanced tissue preservation after SCI

Funded in: 2018, 2019, 2020


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Problem: There is an unmet need for development of novel treatments for SCI

Target: Excessive lysosomal activity in the acute phase after SCI

Goal: Targeting the lysosomal enzymes will decrease cell death associated with the acute stage tissue damage and therefore it can lead to better recovery after injury

 

Do we need new therapies?

Spinal cord injury (SCI) remains an untreatable and devastating neurological condition that affects adults in the prime time of their life. The current treatment approaches have provided minimal improvement in patients‘ recovery and therefore, there is an unmet need for development of novel treatments for SCI.

 

What is the target?

Physical damage to the spinal cord results in generation of free radicals that contribute to cell death and tissue degeneration in acute phase of SCI. This is often mediated by overactivation of lysosomes or the “cellular suicide bags“. Lysosomes are small organelles inside the cells that are packed with damaging enzymes. In normal cells, lysosomes are used for removal of old proteins and cellular debris such as old organelles. The lysosomal enzymes are normally synthesized as non-active enzymes but will be activated when lysosomes are ruptured. Excessive generation of free radicals can damage the lysosomal membrane which leads to spillage of the enzymes. Activation of these enzymes lyse other organelles and metabolic machinery leading to cell death. Excessive cell death and tissue damage is the main cause of disability in SCI patients. 

 

Who are we?

We are a team of researchers with longstanding interest and expertise in SCI. We strive to understand disease mechanisms and develop repair and regeneration strategies for SCI. For this project we will utilize specific non-toxic inhibitors for selective inhibition of lysosomal enzymes to unravel lysosomal mechanisms of cell death and to evaluate its potential as neuroprotective treatment for SCI.

 

Potential outcome?

We anticipate that targeting the lysosomal enzymes will decrease cell death associated with the acute stage tissue damage and therefore it can lead to better recovery after injury. If this strategy proven to be promising in our preclinical models, the approach can be potentially used for future clinical studies.