This category page covers biotechnology and pharmaceutical companies developing therapies that target TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) for Parkinson's disease (PD) and related alpha-synucleinopathies. TREM2 is a receptor expressed primarily on microglia in the brain that plays a critical role in phagocytosis, neuroinflammation regulation, and clearance of pathological protein aggregates.
While most TREM2 therapeutic development has focused on Alzheimer's disease, there is growing evidence that TREM2 modulation may also benefit Parkinson's disease patients by:
TREM2 is a cell surface receptor belonging to the immunoglobulin superfamily, primarily expressed on microglia and peripheral macrophages. In neurodegenerative diseases, TREM2 signaling influences several critical microglial functions:
| Function | TREM2 Role in PD |
|---|---|
| Phagocytosis | Enhances clearance of alpha-synuclein aggregates |
| Neuroinflammation | Modulates pro-inflammatory cytokine production |
| Cell survival | Promotes microglial survival and proliferation |
| Lipid metabolism | Processes lipid ligands from damaged neurons |
Genetic studies have identified TREM2 variants associated with increased PD risk, similar to Alzheimer's disease findings. The R47H variant (rs75932628) has been linked to increased risk in both European and Chinese populations[1][@jiang2024].
Soluble TREM2 (sTREM2) in cerebrospinal fluid has emerged as a biomarker for microglial activation in PD. Studies show sTREM2 levels correlate with disease progression and may predict therapeutic response[2].
Pipeline: AL002 (TREM2 agonist)
Alector is a pioneering company in the immuno-neurology space, developing innate immune checkpoint modulators for neurodegeneration. While their lead program AL002 is primarily in Alzheimer's disease trials, the company has acknowledged preclinical work in Parkinson's disease models.
See Alector for full company profile.
Pipeline: DNL919, DNL126 (TREM2 agonists)
Denali Therapeutics has a robust TREM2 program leveraging their Brain Transport Vehicle (BTV) platform for enhanced CNS penetration.
See Denali Therapeutics for full company profile.
Pipeline: VIG-100, VIG-106 (TREM2 agonists)
Vigil Neuroscience focuses on microglia-targeting therapies for neurodegenerative diseases.
See Vigil Neuroscience for full company profile.
Pipeline: Research programs in TREM2 modulation for PD
Aleza Therapeutics is developing TREM2-targeted approaches specifically for Parkinson's disease.
See Aleza Therapeutics for full company profile.
Pipeline: AL002 (in partnership with Genentech)
AC Immune collaborates with Genentech on TREM2 programs.
See AC Immune for full company profile.
| Company | Drug | Mechanism | Indication | Stage | Clinical Trial |
|---|---|---|---|---|---|
| Alector/Genentech | AL002 | TREM2 agonist mAb | AD | Phase 2 | NCT05189193 |
| Denali | DNL919 | TREM2 agonist (BTV) | AD | Phase 1 | — |
| Vigil Neuroscience | VIG-100 | TREM2 agonist mAb | PD/AD | Phase 1 | — |
| Vigil Neuroscience | VIG-106 | TREM2 agonist mAb | PD/AD | Phase 1 | — |
TREM2 therapy for PD faces several challenges:
The TREM2 space for PD is earlier than AD, with no dedicated PD Phase 2 trials as of early 2026. However, the strong biological rationale and AD trial learnings position this as a promising approach.
Christensen A, et al. TREM2 genetic variants and Parkinson's disease risk in European populations. Brain. 2024. ↩︎
Zhao Y, et al. Soluble TREM2 in cerebrospinal fluid as a biomarker in Parkinson's disease. Neurology. 2024. ↩︎