Astrocyte-Targeted Parkinson's Disease Therapies

Overview

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

Overview

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

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

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)

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

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)

• GDNF promotes dopaminergic neuron survival and supports astrocyte metabolic functions
• BDNF supports neuronal function and plasticity, with cross-talk to astrocyte homeostasis

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)

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

Astrocyte Metabolic Coupling

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

External Links

• [Michael J. Fox Foundation - Astrocyte Research](https://www.michaeljfox.org/)
• [CSF1R Modulation - Novel Therapy Approach](/ideas/csf1r-modulation-microglia-reset)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving Astrocyte-Targeted Parkinson's Disease Therapies discovered through SciDEX knowledge graph analysis: