Our PNAS article showed the mechanisms of neuronal and beta cell death in Wolfram syndrome. We discovered the following three phenomena in Wolfram syndrome.
1. Increased cytoplasmic calcium levels (decreased endoplasmic reticulum calcium levels)
2. Hyper-activation of calpain 2 due to the increased calcium levels
3. Increased cell death due to the calpain 2 hyper-activation
We discovered that dantrolene can prevent #1, which subsequently prevents #2 and #3. In theory, any drugs that can prevent #1 should be able to prevent #2 and #3. We are conducting dose-escalation studies for dantrolene. In parallel, we need to EXPAND OUR PIPELINE of drugs that can prevent #1, #2, and #3. We need a back-up plan.
Thank you for reading this blog. I hope you have a wonderful weekend.