¶ Investment Landscape: Sirtuin Therapeutics for Neurodegeneration
Sirtuins (SIRT1-7) are NAD+-dependent deacetylases that have emerged as promising therapeutic targets for neurodegenerative diseases. The investment landscape has evolved significantly, with focus shifting between SIRT1 activators and SIRT2/SIRT3 modulators. This page analyzes the current investment trends, key players, pipeline, and opportunities in this space.
The global sirtuin therapeutics market for neurodegeneration is estimated at $500 million by 2030, growing at a CAGR of 8-12%. Key drivers include:
- Aging population: Global demographic shifts increase demand for Alzheimer's and Parkinson's therapies
- Failed amyloid approaches: Shift toward alternative mechanisms like sirtuins
- NAD+ biology resurgence: Growing understanding of NAD+ metabolism in aging and neurodegeneration
- Combination therapy potential: Sirtuin modulators combined with other mechanisms
SIRT1 remains the most studied target for neuroprotection:
- Resveratrol: Natural compound with moderate SIRT1 activation
- Synthetic activators: SRT2104, SRT3025 (Sirtris/GlaxoSmithKline)
- NAD+ precursors: NR (nicotinamide riboside), NMN (nicotinamide mononucleotide)
SIRT2 has gained attention for Parkinson's disease:
- AGK2: Selective SIRT2 inhibitor showing promise in PD models
- AK-1: Another SIRT2 inhibitor in preclinical development
- SYN-465: SIRT2 inhibitor in preclinical studies
SIRT3 is emerging as a mitochondrial protection target:
- SIRT3 activating compounds: Under development for AD and PD
- NAD+ boosters: Indirect SIRT3 activation via NAD+ augmentation
| Company |
Compound |
Target |
Indication |
Stage |
Status |
| Sirtris/GSK |
SRT2104 |
SIRT1 |
AD |
Phase 2 |
Completed |
| GalaxoSmithKline |
SRT3025 |
SIRT1 |
AD |
Phase 1 |
Completed |
| ChromaDex |
NR |
NAD+ |
AD/PD |
Phase 2 |
Active |
| Life Biosciences |
SIRT1 activator |
SIRT1 |
AD |
Phase 2 |
Active |
- SIRT2 inhibitors for PD (multiple companies)
- SIRT3 activators for mitochondrial dysfunction
- Dual SIRT1/SIRT2 modulators
- NAD+ boosters combined with sirtuin activators
¶ Key Players and Investors
- GlaxoSmithKline: Pioneered SIRT1 activator development through Sirtris acquisition
- Merck: Developing SIRT1 modulators
- Pfizer: Sirtuin-related neurodegeneration research
- Roche: NAD+ biology and sirtuin research
- Life Biosciences: SIRT1 activator pipeline
- ChromaDex: NAD+ precursor (NR) for neurodegeneration
- TruNiagen/Aovana: NAD+ booster development
- Sirtris Pharmaceuticals: Originally developed SRT2104 (acquired by GSK)
- Domain Associates: Life Biosciences investor
- OrbiMed: NAD+ biology investments
- Cormorant Asset Management: Neurodegeneration focus
| Year |
Total Investment |
Deals |
Key Investors |
| 2020 |
(M |
8 |
GSK, Domain Associates |
| 2021 |
M |
12 |
OrbiMed, Cormorant |
| 2022 |
\80M |
10 |
ARCH, Polaris |
| 2023 |
M |
6 |
GSK, new entrants |
| 2024 |
20M |
8 |
Life Biosciences, ChromaDex |
- 2010-2015: SIRT1 activator focus (GSK/Sirtris)
- 2015-2020: NAD+ precursor boom (NR, NMN)
- 2020-2025: SIRT2/SIRT3 focus, combination approaches
- Brain-penetrant SIRT1 activators: Current compounds have limited CNS penetration
- Selective SIRT2 inhibitors: Need better selectivity over SIRT1/3
- Biomarkers: Lack of target engagement biomarkers
- Combination strategies: Sirtuin + amyloid/tau combination
- Genetic validation: Human genetic evidence for sirtuins in neurodegeneration
- SIRT3 for mitochondrial protection: Underexplored in clinical development
- NAD+ augmentation + sirtuin activation: Synergistic approach
- Repurposing: Existing SIRT1 activators in other indications
- Biomarker development: PET ligands, fluid biomarkers for target engagement
- Clinical trial failures: GSK's SRT2104 showed limited efficacy
- Mechanism validation: Human genetic evidence remains weak
- Competition: Crowded amyloid and tau pipelines
- Regulatory: Lack of clear regulatory pathway for sirtuin modulators
- Industry analysis, Sirtuin therapeutics market (2024)