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<div class="infobox-header">Vandria SA</div>
<div class="infobox-row"><strong>Headquarters:</strong> Geneva, Switzerland</div>
<div class="infobox-row"><strong>Founded:</strong> 2018</div>
<div class="infobox-row"><strong>Focus:</strong> Mitochondrial therapeutics</div>
<div class="infobox-row"><strong>Status:</strong> Private</div>
</div>
Overview
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...<div class="infobox infobox-company">
<div class="infobox-header">Vandria SA</div>
<div class="infobox-row"><strong>Headquarters:</strong> Geneva, Switzerland</div>
<div class="infobox-row"><strong>Founded:</strong> 2018</div>
<div class="infobox-row"><strong>Focus:</strong> Mitochondrial therapeutics</div>
<div class="infobox-row"><strong>Status:</strong> Private</div>
</div>
Overview
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Vandria SA is a Swiss biotechnology company developing novel therapeutics that target mitochondrial function and cellular energetics in age-related neurodegenerative diseases, including both Alzheimer's disease and Parkinson's disease. Founded in 2018 and headquartered in Geneva, Switzerland, Vandria focuses on modulating mitochondrial quality control mechanisms to protect neurons from degeneration["@vandria"].
The company's lead program, VNA-318, targets mitochondrial dysfunction—a fundamental contributor to neuronal death in Alzheimer's disease. A second program, VNA-100, is specifically directed at Parkinson's disease and targets mitophagy defects that are central to dopaminergic neuron degeneration["@alzforum"].
Pipeline Overview
| Program | Mechanism | Indication | Phase | Status |
|---------|-----------|------------|-------|--------|
| VNA-318 | Mitochondrial modulator | Alzheimer's Disease | Phase 1 | Active |
| VNA-100 | Mitophagy inducer | Parkinson's Disease | Preclinical | IND-enabling |
Parkinson's Disease Program: VNA-100
VNA-100 represents Vandria's entry into Parkinson's disease, leveraging the company's expertise in mitochondrial quality control to address PD-specific pathology[@langston2023].
Parkinson's Disease Rationale
PD is uniquely tied to mitochondrial dysfunction through both genetic and environmental evidence:
- Genetic evidence: Mutations in PINK1, PARKIN, and DJ-1 cause familial PD through defects in mitophagy
- Environmental evidence: MPTP and certain pesticides cause PD-like syndrome via mitochondrial Complex I inhibition
- Sporadic PD: Complex I deficiency is consistently observed in sporadic PD substantia nigra
- Convergence: Multiple genetic risk factors (GBA, ATP13A2) converge on lysosomal-mitochondrial axis
Mechanism in PD
VNA-100 targets the PINK1-PARKIN mitophagy pathway, which is directly impaired in familial PD:
- PINK1 activation: Stabilizes on damaged mitochondrial outer membrane
- PARKIN recruitment: Activates E3 ubiquitin ligase activity
- Autophagy receptor recruitment: Links ubiquitinated mitochondria to autophagosomes
- Lysosomal fusion: Results in mitochondrial degradation and renewal
Preclinical Development
VNA-100 is in IND-enabling studies, with the program focused on:
- Demonstrating oral bioavailability and CNS penetration
- Validating mitophagy activation in relevant PD models
- Establishing dose-range finding for efficacy studies
- Biomarker development to track mitophagy in clinical setting
Vandria's Mitochondrial Focus in Parkinson's Disease
Vandria is also exploring targeted protein degradation approaches including monobody-based PROTAC technologies for Parkinson's disease. This first-in-class approach aims to selectively degrade pathological proteins using monobody scaffolds linked to E3 ligase recruiters.
The Role of Mitochondrial Dysfunction in PD
Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. These neurons have exceptionally high energy demands due to their pacemaking activity and extensive axonal arborizations, making them particularly vulnerable to mitochondrial dysfunction[@langston2023].
Key mitochondrial mechanisms in PD include:
- Complex I deficiency: Reduced complex I activity is observed in PD brains and is linked to the pathogenesis of both sporadic and genetic forms of PD[@schapira1989]
- PINK1-Parkin pathway dysfunction: Mutations in PINK1 and PARK2 genes cause autosomal recessive PD by impairing mitophagy—the selective autophagy pathway that removes damaged mitochondria[@pickrell2015]
- Mitochondrial DNA damage: Accumulation of mitochondrial DNA mutations in dopaminergic neurons contributes to progressive respiratory chain dysfunction[@bendor2013]
- Altered mitochondrial dynamics: Changes in fission and fusion processes lead to accumulation of dysfunctional mitochondria[@van2015]
VNA-100: Mitophagy Enhancement for PD
VNA-100 is Vandria's preclinical program targeting Parkinson's disease. Unlike VNA-318, which has a broader mitochondrial mechanism, VNA-100 is specifically designed to enhance mitophagy—the cellular process responsible for removing damaged mitochondria.
Mechanism of Action:
- Mitophagy activation: Promotes the clearance of damaged mitochondria through the PINK1-Parkin pathway
- Mitochondrial quality control: Enhances the selective removal of dysfunctional mitochondria before they can release pro-apoptotic factors
- Dopaminergic neuron protection: Specifically targets the vulnerability of substantia nigra neurons to mitochondrial stress
- Energy restoration: Improves mitochondrial ATP production in neurons with impaired respiratory chain function
Rationale:The rationale for mitophagy enhancement in PD is supported by genetic evidence. PINK1 and Parkin mutations cause early-onset autosomal recessive PD, demonstrating that impaired mitophagy is sufficient to cause dopaminergic neuron degeneration[@pickrell2015]. Similarly, mutations in GBA (glucocerebrosidase) which increase the risk of PD, are associated with impaired mitochondrial function and autophagy[@gegg2020].
Preclinical Development
VNA-100 is currently in preclinical development with IND-enabling studies underway. The program builds on Vandria's platform capabilities:
- In vitro models: iPSC-derived dopaminergic neurons from PD patients
- In vivo models: MPTP-induced parkinsonism models and genetic PD models
- Biomarkers: Mitophagy flux assays, mitochondrial function markers
Lead Program: VNA-318 (Alzheimer's Disease)
Mechanism of Action
VNA-318 is a first-in-class small molecule targeting mitochondrial function:
- Mitochondrial dynamics: Modulates fission and fusion processes
- Biogenesis: Promotes creation of new healthy mitochondria
- Autophagy (mitophagy): Enhances clearance of damaged mitochondria
- Metabolic support: Improves cellular energetics and ATP production
- Neuroprotection: Protects neurons from mitochondrial dysfunction-induced death
Clinical Development
VNA-318 entered Phase 1 clinical trials in 2024, with first-in-human studies in healthy volunteers[@alzforum]. The trial program includes:
- Phase 1a: Single ascending dose in healthy volunteers
- Phase 1b: Multiple ascending dose in early AD patients
- Biomarkers: Mitochondrial function and neuroinflammatory markers
Rationale
Mitochondrial dysfunction is an early and central event in Alzheimer's disease:
- Energy deficit: Neurons require high energy; mitochondrial failure compromises function
- Oxidative stress: Damaged mitochondria produce excess reactive oxygen species (ROS)
- Apoptosis: Mitochondrial outer membrane permeabilization triggers neuronal death
- Bioenergetic crisis: Brain shows impaired glucose metabolism early in AD
VNA-318 addresses these issues through:
- Enhancement of mitophagy to clear damaged mitochondria
- Promotion of mitochondrial biogenesis
- Improvement of cellular energetics
Vandria's platform is built on understanding mitochondrial biology:
Key Capabilities
| Platform | Application |
|----------|-------------|
| Mitochondrial assays | OCR, ATP, membrane potential |
| Cellular models | iPSC-derived neurons |
| In vivo models | Mitochondrial dysfunction models |
Academic Collaborations
Vandria maintains collaborations with leading Swiss academic institutions including the University of Geneva and EPFL[@vandria].
Corporate Status
Vandria SA is a privately held company based in Geneva, Switzerland, with funding from Swiss and international venture capital investors[@vandria].
Cross-References
- [Mitochondrial Dysfunction in Parkinson's Disease](/mechanisms/mitochondrial-dysfunction-parkinsons)
- [Mitochondrial Quality Control](/mechanisms/mitochondrial-quality-control)
- [PINK1-Parkin Pathway](/mechanisms/pink1-parkin-pathway)
- [Mitophagy in Neurodegeneration](/mechanisms/mitophagy-neurodegeneration)
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Mitochondrial Therapeutics](/therapeutics/mitochondrial-therapeutics)
- [Mitochondrial Dysfunction in Parkinson's Disease](/mechanisms/pd-mitochondrial-dysfunction)
- [PINK1 Gene](/genes/pink1)
- [Parkin Gene](/genes/parkin-prkn)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
References
Vandria SA, Corporate Website (n.d.)
ALZFORUM Therapeutics Database, Vandria SA (n.d.)
[Langston RG, et al, (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/25877818/)
[Schapira AH, et al, (1989) (1989)](https://pubmed.ncbi.nlm.nih.gov/2564122/)
[Pickrell AM, Youle RJ, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/2564122/)
[Bendor JT, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/24389468/)
[van der Merwe C, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25589637/)
[Gegg ME, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/31625550/)
[Unknown, Mitochondrial Complex I Deficiency in PD - Nature Reviews Neurology (n.d.)](https://doi.org/10.1038/s41582-023-00701-6)