This category page covers biotechnology and pharmaceutical companies developing sirtuin-targeted therapies for Alzheimer's disease. Sirtuins (SIRT1-7) are NAD+-dependent deacetylases that play critical roles in mitochondrial function, DNA repair, stress resistance, and cellular homeostasis—all processes impaired in Alzheimer's disease.
For the main mechanism page, see SIRT1 Signaling Pathway in Alzheimer's Disease.
- Direct SIRT1 activators (resveratrol, synthetic compounds like SRT2104)
- NAD+ precursors (nicotinamide riboside, NMN) that enhance SIRT1 activity indirectly
- Mechanisms: PGC-1α deacetylation → mitochondrial biogenesis; FOXO deacetylation → stress resistance; tau deacetylation → reduced aggregation; NF-κB deacetylation → reduced neuroinflammation
- SIRT2 inhibitors may protect against AD progression
- Target α-synuclein toxicity (relevant for comorbid PD/LBD)
- Reduce inflammatory responses
- Mitochondrial sirtuin targeting
- SOD2 activation → reduced oxidative stress
- IDH2 activation → improved mitochondrial metabolism
- Epigenetic regulation of mitochondrial genes
| Company |
Focus |
Programs |
Status |
| GSK |
SIRT1 direct activators |
SRT2104 (historical), SRT3025 |
Historical/Clinical |
| Company |
Focus |
Programs |
Page |
| ChromaDex |
NAD+ precursors |
NR-002, Tru NIAGEN |
ChromaDex |
| Life Biosciences |
SIRT1 activator |
LB-SIRT1 program |
Life Biosciences |
| Elysium Health |
NAD+ supplements |
Basis |
— |
| Vivoryon Therapeutics |
SIRT1 modulators |
PQ912 |
Vivoryon |
flowchart TD
subgraph Direct_Activation
A["SIRT1 Activators"] --> B["GSK (SRT2104)"]
A --> C["Life Biosciences"]
A --> D["Vivoryon"]
end
subgraph NAD_Augmentation
E["NAD+ Precursors"] --> F["ChromaDex (NR)"]
E --> G["Elysium Health (NIAGEN)"]
end
subgraph Mechanisms
B --> H["Mitochondrial Biogenesis"]
C --> H
F --> I["Cellular NAD+↑"]
G --> I
D --> J["Synaptic Protection"]
end
subgraph Outcomes
H --> K["Neuroprotection"]
I --> K
J --> K
end
| Company |
Compound |
Target |
Mechanism |
Phase |
Indication |
| ChromaDex |
NR-002 |
SIRT1 (indirect) |
NAD+ augmentation |
Phase 2 |
Alzheimer's disease |
| GSK (historical) |
SRT2104 |
SIRT1 |
Direct activation |
Phase 2 |
Alzheimer's disease |
| Life Biosciences |
LB-SIRT1 |
SIRT1 |
Direct activation |
Discovery |
Alzheimer's disease |
| Vivoryon |
PQ912 |
SIRT1 |
Direct activation |
Phase 2 |
Alzheimer's disease |
¶ Market Landscape
The sirtuin modulator field for Alzheimer's disease has evolved through several phases:
- 2006-2012: Sirtris/GSK pioneered direct SIRT1 activators (resveratrol, SRT2104)
- 2012-2020: Shift to NAD+ precursors (nicotinamide riboside, NMN) as indirect activators
- 2020-present: Combination approaches and next-generation SIRT1 modulators
- Major pharma (GSK) has reduced direct SIRT1 activator investment
- Biotech focus on NAD+ augmentation (ChromaDex, Elysium)
- Academic/industry partnerships for biomarker development
- Growing interest in combination therapies (SIRT1 + other mechanisms)
- Brain penetration: Current SIRT1 activators have limited CNS delivery
- Target engagement biomarkers: Need better biomarkers for SIRT1 activity
- Combination strategies: Sirtuin + other mechanisms (e.g., amyloid, tau)
- Genetic validation: Human genetic evidence for sirtuins in AD remains limited
- Clinical efficacy: Translation from preclinical models to human trials has been challenging