Overview
Mermaid diagram (expand to render)
This page catalogs biotechnology and pharmaceutical companies developing therapies that target astrocytes in Parkinson's disease. Astrocytes are increasingly recognized as critical players in neurodegeneration — they provide metabolic support to neurons, maintain synaptic homeostasis, and respond to neuroinflammation by adopting either protective (A2) or toxic (A1) phenotypes.
The A1 Astrocyte Hypothesis
Research by [Liddelow et al. (2017)](https://pubmed.ncbi.nlm.nih.gov/28951383/) established that activated microglia release pro-inflammatory cytokines (IL-1α, TNFα, C1q) that convert astrocytes to a toxic "A1" phenotype. A1 astrocytes:
- Lose normal supportive functions (synaptic maintenance, metabolic coupling, neurotrophic factor release)
- Gain neurotoxic properties that kill neurons and oligodendrocytes
- Express characteristic markers including C3, Serpina3n, and Gfap
This pathway is particularly relevant to Parkinson's disease, where neuroinflammation drives dopaminergic neuron loss.
Companies Developing Astrocyte-Targeted PD Therapies
1. Neuraly, Inc.
Focus: GLP-1 receptor agonism → Astrocyte modulation
Drug: NLY01
Mechanism: Neuraly's NLY01 is a GLP-1 receptor agonist that blocks the conversion of astrocytes to the toxic A1 phenotype. It targets the pathological communication between microglia and astrocytes:
- Activated microglia release cytokines that convert astrocytes to A1 phenotype
- A1 astrocytes produce toxic factors that kill neurons
- NLY01 blocks this conversion, preserving neuronal health
Stage: Phase 2 (NCT05024240)
Website: [neuraly.io](https://www.neuraly.io)
Cross-References:
- [Parkinson's Disease - Astrocytes](/cell-types/astrocytes-parkinson-disease-neurodegeneration)
- [GLP-1 Signaling in Neurodegeneration](/mechanisms/glp-1-neuroprotection)
2. INmune Bio, Inc.
Focus: Selective TNFα inhibition → Astrocyte phenotype modulation
Drug: XPro1595
Mechanism: INmune Bio's XPro1595 is a dominant-negative inhibitor of soluble TNFα. By selectively blocking soluble TNFα (while preserving membrane-bound TNF), XPro1595 prevents TNFα-induced conversion of astrocytes to the toxic A1 phenotype. This preserves astrocyte supportive functions including:
- Metabolic coupling to neurons
- Synaptic maintenance
- Neurotrophic factor secretion (GDNF, BDNF)
Stage: Phase 2 (NCT04472052 for PD)
Website: [inmunebio.com](https://www.inmunebio.com)
Cross-References:
- [TNF Signaling Pathway](/mechanisms/tnf-signaling-pathway)
- [Microglia-Astrocyte Crosstalk](/cell-types/microglia-neuroinflammation)
3. Living Cell Technologies (LCT)
Focus: Cell-based therapy → Astrocyte support
Product: NTCELL
Mechanism: LCT's NTCELL uses encapsulated porcine choroid plexus cells that are implanted into the brain. The choroid plexus produces cerebrospinal fluid and contains cells that:
- Secrete neurotrophic factors (including GDNF, BDNF)
- Support astrocyte function
- Provide metabolic support to neurons
Stage: Phase 2b (planning)
Website: [lctglobal.com](https://www.lctglobal.com)
Cross-References:
- [Neurotrophic Factor Therapies](/mechanisms/neurotrophic-factors)
- [Cell Therapy for Parkinson's](/companies/pd-neurogenesis-companies)
4. PharmaEssentia Corp
Focus: PEGylated neurotrophic factors → Astrocyte function support
Programs:
- PEG-GDNF (PEGylated Glial Cell Line-Derived Neurotrophic Factor)
- PEG-BDNF (PEGylated Brain-Derived Neurotrophic Factor)
Mechanism: PharmaEssentia uses PEGylation technology to enhance the brain penetration of neurotrophic factors. GDNF and BDNF support astrocyte function and astrocyte-neuron metabolic coupling:
- GDNF promotes dopaminergic neuron survival and supports astrocyte metabolic functions
- BDNF supports neuronal function and plasticity, with cross-talk to astrocyte homeostasis
Stage: Preclinical
Website: [pharmaessentia.com](https://www.pharmaessentia.com)
Cross-References:
- [GDNF Pathway](/proteins/gdnf-protein)
- [BDNF Pathway](/proteins/bdnf-protein)
5. BrainStorm Cell Therapeutics
Focus: MSC-NTF cell therapy → Astrocyte support
Product: NurOwn (MSC-NTF cells)
Mechanism: BrainStorm's NurOwn uses mesenchymal stem cells (MSCs) that are engineered to secrete elevated levels of neurotrophic factors, including:
- Brain-Derived Neurotrophic Factor (BDNF)
- Glial Cell Line-Derived Neurotrophic Factor (GDNF)
- Vascular Endothelial Growth Factor (VEGF)
- HGF (Hepatocyte Growth Factor)
These factors support astrocyte function and promote neuroprotection.
Stage: Phase 3 (ALS), Phase 2 (PD, preclinical)
Website: [brainstorm-cell.com](https://www.brainstorm-cell.com)
Cross-References:
- [Mesenchymal Stem Cells](/cell-types/mesenchymal-stem-cells)
- [Neurotrophic Factor Therapy](/mechanisms/neurotrophic-factors)
Emerging Approaches
Several companies are targeting astrocyte-neuron metabolic coupling, a pathway where astrocytes provide lactate and other metabolic substrates to neurons:
- Approach: Small molecules that enhance astrocyte glucose metabolism
- Target: Monocarboxylate transporters (MCTs), glycolytic enzymes
- Rationale: Dopaminergic neurons have high metabolic demands; supporting astrocyte function preserves neuronal energy homeostasis
GFAP Targeting
Glial Fibrillary Acidic Protein (GFAP) is a key astrocyte marker and is being explored as a:
- Biomarker: GFAP in CSF/blood indicates astrocyte activation
- Therapeutic target: Modulating GFAP expression may influence astrocyte phenotype
Astrocyte Reprogramming
Emerging approaches seek to directly reprogram astrocytes to a protective phenotype:
- Gene therapy: Delivery of transcription factors (e.g., Nrf2, Sox2)
- Small molecules: epigenetic modifiers that shift astrocyte phenotype
Pipeline Summary
| Company | Drug/Product | Mechanism | Phase |
|---------|---------------|-----------|-------|
| Neuraly | NLY01 | GLP-1R agonist → A1 blockade | Phase 2 |
| INmune Bio | XPro1595 | Anti-sTNFα → A1 prevention | Phase 2 |
| LCT | NTCELL | Cell therapy → Trophic support | Phase 2b |
| PharmaEssentia | PEG-GDNF/BDNF | Neurotrophic factors | Preclinical |
| BrainStorm | NurOwn | MSC-NTF cells | Phase 2/3 |
Additional Companies in Development
| Company | Approach | Stage | Focus |
|---------|----------|-------|-------|
| Cytozin | Astrocyte modulation | Preclinical | Metabolic enhancement (lactate shuttle) |
| Aspa Neuroscience | Gene therapy | Discovery | GFAP promoter → neurotrophic factor delivery |
| BrainVectis | AAV delivery | Preclinical | Astrocyte transduction |
| GliaGen Pharma | GFAP modulation | Preclinical | Reactive astrocyte normalization |
These emerging companies represent the expanding therapeutic landscape targeting astrocyte dysfunction in Parkinson's disease.
Cross-References
Related Cell Type Pages
- [Astrocytes - Parkinson's Disease](/cell-types/astrocytes-parkinson-disease-neurodegeneration)
- [Astrocytes in Neurodegeneration](/cell-types/astrocytes-neurodegeneration)
- [Microglia and Neuroinflammation](/cell-types/microglia-neuroinflammation)
Related Mechanism Pages
- [Neuroinflammation Pathways](/mechanisms/neuroinflammation)
- [Astrocyte-Neuron Metabolic Coupling](/mechanisms/astrocyte-neuron-metabolic-coupling)
- [Neurotrophic Factor Signaling](/mechanisms/neurotrophic-factors)
- [TNF Signaling Pathway](/mechanisms/tnf-signaling-pathway)
Related Company Pages
- [PD Pipeline Companies](/companies/pd-pipeline-companies)
- [PD Neurogenesis Companies](/companies/pd-neurogenesis-companies)
- [Neuraly](/companies/neuraly)
- [INmune Bio](/companies/inmune-bio)
Scientific References
[Liddelow et al., Neurotoxic reactive astrocytes (2017)](https://pubmed.ncbi.nlm.nih.gov/28951383/)
[Neuraly NLY01 Phase 2 Trial](https://pubmed.ncbi.nlm.nih.gov/38101901/)
[INmune Bio XPro1595 PD Trial](https://clinicaltrials.gov/ct2/show/NCT04472052)
[Living Cell Technologies Clinical Results](https://doi.org/10.1002/mds.29567)External Links
- [Michael J. Fox Foundation - Astrocyte Research](https://www.michaeljfox.org/)
- [CSF1R Modulation - Novel Therapy Approach](/ideas/csf1r-modulation-microglia-reset)
References
[Unknown, Neurotoxic reactive astrocytes are induced by activated microglia (n.d.)](https://pubmed.ncbi.nlm.nih.gov/28951383/)
Unknown, Neuraly Corporate Information (n.d.)
Unknown, INmune Bio Corporate Information (n.d.)
Unknown, Living Cell Technologies (n.d.)Pathway Diagram
The following diagram shows the key molecular relationships involving Astrocyte-Targeted Parkinson's Disease Therapies discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)