Relyvrio (Sodium Phenylbutyrate Taurursodiol) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
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Sodium Phenylbutyrate/Taurursodiol (Relyvrio) for Amyotrophic Lateral Sclerosis
Relyvrio (Sodium Phenylbutyrate Taurursodiol) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
Sodium phenylbutyrate/taurursodiol (Relyvrio®; also known as AMX0035) is an FDA-approved combination therapy for amyotrophic lateral sclerosis (ALS). Approved in 2022, Relyvrio represents a novel approach to ALS treatment by targeting multiple pathological pathways simultaneously.[@fda2022] The drug was developed by Amylyx Pharmaceuticals and represents one of the few disease-modifying therapies available for ALS, alongside riluzole, edaravone, and antisense oligonucleotides (tofersen for SOD1-associated ALS). [@sodium2004]
Mechanism of Action
Relyvrio combines two compounds with complementary mechanisms that target both endoplasmic reticulum (ER) stress and mitochondrial dysfunction—two central pillars of ALS pathogenesis: [@tauroursodeoxycholic2003]
Reduces ER stress: Decreases [unfolded protein response](/entities/unfolded-protein-response) (UPR) activation, which is chronically elevated in ALS motor [neurons](/entities/neurons)
Promotes protein folding: Enhances cellular protein quality control mechanisms through chaperone upregulation
Neuroprotective effects: Reduces oxidative stress and mitochondrial dysfunction through transcriptional regulation[@sodium2004]
Chemical chaperone: Helps stabilize mutant proteins and reduces toxic protein aggregation
Taurursodiol (TUDCA - Tauroursodeoxycholic Acid)
Mitochondrial protector: Stabilizes mitochondrial membrane potential and prevents permeability transition
Reduces [apoptosis](/mechanisms/apoptosis): Inhibits mitochondrial-dependent cell death pathways including cytochrome c release
Anti-inflammatory: Modulates microglial activation and reduces neuroinflammation
Improves cellular energetics: Enhances ATP production and mitochondrial function[@tauroursodeoxycholic2003]
Bcl-2 family interaction: Modulates pro-apoptotic and anti-apoptotic Bcl-2 proteins
Combined Synergistic Effect
The combination provides synergistic neuroprotection by: [@trial2020]
Reducing neuronal death from multiple simultaneous insults
Targeting both protein aggregation (ER stress) and energy failure (mitochondrial dysfunction)
Modulating neuroinflammation through multiple pathways
Supporting cellular homeostasis under pathological stress conditions[@trial2020]
Clinical Evidence
CENTAUR Trial (Phase 2)
The CENTAUR trial (NCT03000196) was a landmark study that led to Relyvrio's approval: [@primary2020]
The study of Relyvrio (Sodium Phenylbutyrate Taurursodiol) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Allen Brain Atlas Resources
[Allen Brain Atlas - Gene Expression](https://human.brain-map.org/) - Search for gene expression data across brain regions