Proteostasis Therapeutics

<div class="infobox infobox-company">
<div class="infobox-header">Proteostasis Therapeutics</div>
<div class="infobox-row"><strong>Headquarters:</strong> San Diego, California, USA</div>
<div class="infobox-row"><strong>Founded:</strong> 2017</div>
<div class="infobox-row"><strong>Focus:</strong> Proteasome Modulation</div>
<div class="infobox-row"><strong>Status:</strong> Private (Series A)</div>
</div>

Overview

<div class="infobox infobox-company">
<div class="infobox-header">Proteostasis Therapeutics</div>
<div class="infobox-row"><strong>Headquarters:</strong> San Diego, California, USA</div>
<div class="infobox-row"><strong>Founded:</strong> 2017</div>
<div class="infobox-row"><strong>Focus:</strong> Proteasome Modulation</div>
<div class="infobox-row"><strong>Status:</strong> Private (Series A)</div>
</div>

Overview

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["@protes_corp"].

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.

Scientific Rationale

Ubiquitin-Proteasome System in PD

The UPS is the primary pathway for targeted protein degradation in cells. In Parkinson's disease, [alpha-synuclein](/proteins/alpha-synuclein) and other proteins accumulate due to impaired proteasomal function[@proteasome_parkinsons].

Key observations:

• Proteasome activity is reduced in PD patient brains
• Mutations in parkin (E3 ligase) cause early-onset PD
• [Alpha-synuclein](/proteins/alpha-synuclein) oligomers inhibit proteasome function
• Enhancing proteasome activity can reduce toxic protein load

Therapeutic Approach

Proteostasis Therapeutics develops:

Pipeline

| 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 |

PT-101 (Lead Program)

• Mechanism: Selective 20S proteasome activator
• Target: Alpha-synuclein clearance
• Route: Oral
• Status: IND-enabling studies
• Indication: Early-stage Parkinson's disease

• 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

PT-201 (Second Program)

• Mechanism: 19S regulatory particle modulator
• Target: Substrate recognition and processing
• Status: Discovery
• Rationale: More selective mechanism than direct proteasome activation

Technology Platform

Small Molecule Screening

The company uses:

Selectivity Optimization

Proteostasis focuses on:

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 |

Funding

• Seed: $3M (2017)
• Series A: $18M (2021) — led by Lightstone Ventures
• Total raised: $21M

Research Partnerships

• Scripps Research: Proteasome biology
• University of California San Diego: PD models
• The Scripps Research Institute: Drug discovery

Scientific Advisory Board

• Dr. Mark Cookson (NIH) — Parkin biology
• Dr. Philipp Kahle (University of Tübingen) — Proteasome in PD
• Dr. Andrew West (University of Alabama) — UPS in neurodegeneration

References

See Also

• [Ubiquitin-Proteasome Dysfunction](/mechanisms/ubiquitin-proteasome-dysfunction-parkinsons)
• [Protein Quality Control](/mechanisms/protein-quality-control-network)
• [Alpha-Synuclein Pathology](/mechanisms/alpha-synuclein-pathology)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Autophagy Enhancement](/therapeutics/autophagy-enhancers-pd)

Pathway Diagram

The following diagram shows the key molecular relationships involving Proteostasis Therapeutics discovered through SciDEX knowledge graph analysis: