Proteostasis Therapeutics: Investment Landscape Analysis is a therapeutic approach or intervention being investigated for neurodegenerative diseases. This page reviews the scientific rationale, preclinical and clinical evidence, dosing considerations, and current status of research.
Proteostasis (protein homeostasis) is a fundamental cellular process that maintains protein folding, assembly, and degradation. Dysregulation of proteostasis is a hallmark of neurodegenerative diseases, making proteostasis modulators a promising therapeutic approach.[1]
The proteostasis therapeutics field encompasses multiple mechanisms including molecular chaperones, autophagy inducers, HDAC inhibitors, and NAD+ boosters. Current clinical trial data shows approximately 130 trials targeting proteostasis pathways in neurodegenerative diseases, representing a growing but still underserved investment area.[2]
| Phase | Number of Trials | Percentage |
|---|---|---|
| Phase 1 | 12 | 22% |
| Phase 2 | 28 | 51% |
| Phase 3 | 8 | 15% |
| Completed/Active | 7 | 13% |
mTOR inhibition induces autophagy, a key protein clearance pathway:
| Drug | Company | Phase | Status |
|---|---|---|---|
| Rapamycin | Various | Phase 2 | Completed |
| Everolimus | Novartis | Phase 1/2 | Completed |
| Defactinib | --- | Phase 2 | Recruiting |
Key Sponsors: Great Lakes NeuroTechnologies Inc., University Hospital Montpellier, University of Minnesota
Direct autophagy enhancement:
| Drug | Company | Phase | Status |
|---|---|---|---|
| Trehalose | Various | Phase 1/2/3 | Mixed |
| Metformin | Various | Phase 2 | Completed |
| Carbamazepine | --- | Phase 1 | Completed |
Key Sponsors: Columbia University, Seelos Therapeutics
Histone deacetylase inhibitors modulate proteostasis gene expression:
| Drug | Company | Phase | Status |
|---|---|---|---|
| Sodium Phenylbutyrate/Taurursodiol (AMX0035) | Amylyx | Phase 2/3 | Completed (FDA Approved for ALS) |
| Valproic Acid | Various | Phase 2/3 | Completed |
| Entinostat | --- | Phase 2 | Ongoing |
Key Sponsors: Amylyx Pharmaceuticals Inc., Université de Sherbrooke
NAD+ replenishment supports sirtuin activity and cellular stress resistance:
| Drug | Company | Phase | Status |
|---|---|---|---|
| Nicotinamide Riboside | ChromaDex | Phase 1/2 | Recruiting |
| NMN | Various | Phase 1/2 | Ongoing |
| --- | Haukeland University Hospital | --- | 6 trials |
Key Sponsors: Haukeland University Hospital, McLean Hospital, UC Irvine
Mood stabilizer with autophagy-inducing properties:
| Drug | Company | Phase | Status |
|---|---|---|---|
| Lithium | Various | Phase 1/2/4 | Mixed |
Key Sponsors: SUNY Buffalo, Johns Hopkins
Heat shock protein modulation:
| Drug | Company | Phase | Status |
|---|---|---|---|
| HSP90 Imaging | KU Leuven | Phase 1 | Recruiting |
Key Sponsors: Universitaire Ziekenhuizen KU Leuven
Hippelainen et al. Proteostasis in neurodegenerative disease: emerging mechanisms and therapeutic opportunities. Nature Reviews Drug Discovery. 2023. ↩︎
ClinicalTrials.gov analysis of proteostasis-targeted trials in neurodegeneration. Data accessed March 2026. 2026. ↩︎