Our first in class SIRT3 Agonist has the potential to transform the treatment of AD resulting in a higher cognitive function, better quality of life, and reduction of the finical burden to society for the treatment of this devastating disease.
Alzheimer’s disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking.
- Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, and recent studies have shed new light on the relationship between SIRT3 and mitochondrial function and neuronal activity in AD. Results indicate that SIRT3 dysfunction leads to p53-mediated mitochondrial and neuronal damage in AD.
- Sirt3 mRNA and protein expression in multiple Brain regions were significantly lower in AD compared to those in cognitively normal subjects. We also identified a strong association between Sirt3 and cognition along with a clear inverse correlation between Sirt3 and tau pathology.
- These results that Sirt3 may be a novel player in the pathogenesis of AD. Strategies to modulate Sirt3 expression could disrupt Aβ-induced overproduction of tau and be useful in the treatment of AD.
- ACU-NE1 has also been shown to inhibit the activity of GSK-3β, a key signaling event implicated in tau hyperphosphorylation. Our preliminary studies indicate that ACU-NE1 compound reduces the Amyloid beta levels (BACE 1 activity & Abeta42) in a dose dependent manner.
- We plan to advance ACU-NE1 into additional pre-clinical formulation, pharmacology, and IND enabling toxicology studies