Headquarters: San Diego, California, USA
Founded: 2017
Focus: Proteasome Modulation
Status: Private (Series A)
Proteostasis Therapeutics is a biotechnology company developing small molecule modulators of the ubiquitin-proteasome system (UPS) for the treatment of neurodegenerative diseases. Founded in 2017 in San Diego, the company focuses on enhancing protein clearance through selective modulation of proteasome activity, particularly in Parkinson's disease.
The company was founded based on research showing that partial proteasome activation can enhance clearance of misfolded proteins without causing the cellular stress associated with full proteasome inhibition.
The UPS is the primary pathway for targeted protein degradation in cells. In Parkinson's disease, alpha-synuclein and other proteins accumulate due to impaired proteasomal function.
Key observations:
- Proteasome activity is reduced in PD patient brains
- Mutations in parkin (E3 ligase) cause early-onset PD
- Alpha-synuclein oligomers inhibit proteasome function
- Enhancing proteasome activity can reduce toxic protein load
Proteostasis Therapeutics develops:
- Proteasome activators: Enhance catalytic activity without overactivation
- 19S cap modifiers: Improve substrate processing
- Ubiquitin-like modifiers: Enhance targeting to proteasome
- Combination therapies: With autophagy enhancers
| Drug |
Mechanism |
Phase |
Indication |
| PT-101 |
Proteasome activator |
Preclinical |
Parkinson's disease |
| PT-201 |
19S cap modulator |
Discovery |
Parkinson's disease |
| PT-301 |
UPS-autophagy combo |
Discovery |
Multiple System Atrophy |
- Mechanism: Selective 20S proteasome activator
- Target: Alpha-synuclein clearance
- Route: Oral
- Status: IND-enabling studies
- Indication: Early-stage Parkinson's disease
Preclinical data:
- Increases proteasome activity by 30-50% in neurons
- Reduces alpha-synuclein oligomers in cellular models
- Improves motor function in MPTP mice
- Blood-brain barrier penetration demonstrated
- Mechanism: 19S regulatory particle modulator
- Target: Substrate recognition and processing
- Status: Discovery
- Rationale: More selective mechanism than direct proteasome activation
The company uses:
- Cell-based proteasome activity assays: Primary neurons
- Alpha-synuclein clearance readouts: ELISA and Western blot
- High-content imaging: Aggregate quantification
- Target identification: Chemical biology approaches
Proteostasis focuses on:
- Neuronal vs. peripheral proteasome: CNS-selective compounds
- Immunoproteasome vs. constitutive: Avoiding immune suppression
- Temporal control: Acute vs. chronic dosing strategies
¶ Competitive Landscape
| Company |
Target |
Approach |
Status |
| Proteostasis Therapeutics |
Proteasome |
Small molecule |
Preclinical |
| Araclon |
Proteasome |
Small molecule |
Phase 1 |
| Prothena |
Alpha-synuclein |
Antibody |
Phase 2 |
| Arvinas |
Protein degradation |
PROTAC |
Phase 1 |
- Seed: $3M (2017)
- Series A: $18M (2021) — led by Lightstone Ventures
- Total raised: $21M
- Scripps Research: Proteasome biology
- University of California San Diego: PD models
- The Scripps Research Institute: Drug discovery
- Dr. Mark Cookson (NIH) — Parkin biology
- Dr. Philipp Kahle (University of Tübingen) — Proteasome in PD
- Dr. Andrew West (University of Alabama) — UPS in neurodegeneration