Senolytic therapies represent a novel and promising approach to treating Alzheimer's disease by targeting and eliminating senescent cells that accumulate with aging and in neurodegenerative conditions. These "zombie cells"—cells that have stopped dividing but remain metabolically active—secrete pro-inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP), which drive chronic neuroinflammation and contribute to protein aggregation in AD[1].
The senolytic approach differs fundamentally from other AD therapeutic strategies:
This category page catalogs companies developing senolytic therapies specifically for Alzheimer's disease or expanding their existing senolytic platforms into CNS indications.
Retro Biosciences is a biotechnology company focused on cellular senescence and protein homeostasis in aging and age-related diseases[2]:
| Attribute | Details |
|---|---|
| Focus | Cellular senescence, protein homeostasis |
| Lead Candidate | RB-001 |
| Indication | Alzheimer's disease |
| Stage | Phase 1 |
| Mechanism | Dasatinib + Quercetin (D+Q) combination senolytic |
Scientific Rationale: The D+Q combination targets senescence through multiple pathways:
Notes: Retro Biosciences specifically targets senescence in brain parenchyma and cerebral vasculature, addressing both neuronal and vascular contributions to AD pathogenesis.
Unity Biotechnology is a clinical-stage company developing senolytics for age-related diseases, initially in ophthalmology and orthopedics with expansion into CNS[3]:
| Attribute | Details |
|---|---|
| Focus | Ophthalmology, orthopedic conditions, expanding to CNS |
| Lead Candidates | UBX1325, UBX3457 |
| Stage | Phase 2 (eye/joints), Preclinical for CNS |
| Mechanism | Bcl-2 inhibitor senolytics |
Notes: Unity has demonstrated strong safety data in eye and joint diseases with their lead candidates. The company is developing brain-penetrant analogs of their senolytic molecules for AD and PD applications.
Clever Therapeutics is developing next-generation senolytic approaches:
| Attribute | Details |
|---|---|
| Focus | Targeted senolytic conjugates |
| Mechanism | Antibody-senolytic conjugates for targeted delivery |
| Stage | Preclinical |
Innovation: Clever's approach uses antibody-based targeting to deliver senolytic agents specifically to senescent cells, potentially improving safety and efficacy compared to systemically administered senolytics.
SiWa Therapeutics is exploring novel senolytic combinations:
| Attribute | Details |
|---|---|
| Focus | Novel senolytic combinations |
| Mechanism | Small molecule combinations targeting multiple senescence pathways |
| Stage | Discovery |
Calico is Alphabet's life sciences company focused on aging biology and neurodegeneration:
| Attribute | Details |
|---|---|
| Focus | Aging biology and neurodegeneration |
| Mechanism | Multiple programs including autophagy enhancement |
| Stage | Research |
Approach: Calico's strategy includes understanding fundamental aging mechanisms and developing interventions that address multiple hallmarks of aging, including cellular senescence.
The senolytic field continues to evolve with additional players:
Senolytic drugs work through two main mechanistic approaches[4]:
Drugs that selectively induce apoptosis in senescent cells:
| Mechanism | Example | Status |
|---|---|---|
| Dasatinib + Quercetin | D+Q combination | Phase 1/2 |
| Bcl-2 inhibitors | ABT-263/Navitoclax | Preclinical |
| FOXO4-p53 interference | Peptide-based | Preclinical |
| Spiperone | Selective senolytic | Preclinical |
Drugs that suppress SASP without directly killing senescent cells:
| Mechanism | Example | Status |
|---|---|---|
| mTOR inhibition | Rapamycin | Research |
| JAK inhibition | Ruxolitinib | Research |
| NF-κB inhibition | Various compounds | Research |
Cellular senescence contributes to AD through multiple mechanisms:
| Company | Drug | Phase | Indication | Status |
|---|---|---|---|---|
| Retro Biosciences | RB-001 | Phase 1 | Alzheimer's disease | Pending |
| Unity Biotechnology | UBX3457 | Preclinical | AD/PD | Development |
| Unity Biotechnology | UBX1325 | Phase 2 | Eye disease | Completed |
The connection between cellular senescence and AD is supported by multiple lines of evidence: