Idea ID: inv007-pde5-neuro
Drugs: Sildenafil (Viagra), Tadalafil (Cialis)
Original Indication: Erectile dysfunction, pulmonary hypertension
Repurposed Indication: Alzheimer's Disease, Vascular Cognitive Impairment
Approach: Improve cerebral blood flow and endothelial function
Phosphodiesterase type 5 (PDE5) inhibitors increase cGMP levels:
Vascular contributions to neurodegeneration:
| Finding | Model | Reference |
|---|---|---|
| Improved cerebral blood flow | Mouse AD model | Puzzo et al., 2015 |
| Enhanced memory performance | APP/PS1 mice | Cuellar-Soto et al., 2019 |
| Reduced amyloid pathology | 3xTg-AD mice | Zhang et al., 2017 |
| Neurogenesis enhancement | Adult mice | Tokuda et al., 2013 |
PDE5 inhibitors improve neurodegeneration through:
| Trial | Drug | N | Outcome | Reference |
|---|---|---|---|---|
| Phase 2 (2020) | Sildenafil | 70 | Improved cerebral blood flow | Sampaio et al. |
| Observational | Sildenafil | 500k | Reduced AD risk | Nygaard et al., 2018 |
| Phase 2 | Tadalafil | 100 | No cognitive benefit (small n) | Juliusson et al., 2020 |
| Approach | Company | Stage | Mechanism |
|---|---|---|---|
| PDE5i | Generic | Phase 2 | cGMP enhancement |
| Cerebrolysin | Everest | Approved | Multi-factor |
| Donepezil | Eisai | Approved | Cholinergic |
| Aducanumab | Biogen | Approved | Anti-amyloid |