Headquarters: Wako, Saitama, Japan
Founded: 2023 (RIKEN spin-out)
Focus: Microbiome-based therapies for Parkinson's disease
Website: https://www.riken-seirogan.jp
Overview
Mermaid diagram (expand to render)
Riken Seirogan is a RIKEN spin-out company developing microbiome-based therapeutics that target the gut-brain axis in Parkinson's disease. The company was founded based on landmark research from RIKEN's Laboratory for Microbiome Sciences demonstrating that specific gut bacteria and their metabolites modulate alpha-synuclein pathology, neuroinflammation, and disease progression in Parkinson's disease models["@riken_seirogan2024"].
The gut-brain axis represents a bidirectional communication system between the enteric nervous system, the vagus nerve, and the central nervous system. Parkinson's disease commonly begins with gastrointestinal symptoms — constipation, bloating, and alpha-synuclein deposition in the enteric nervous system — years or decades before motor symptoms emerge. This observation has led to the hypothesis that gut-derived factors may initiate or accelerate alpha-synuclein pathology in the brain. Riken Seirogan's approach leverages this insight to develop novel disease-modifying therapies that restore healthy gut microbiota and reduce pathogenic signaling["@gut_brain_pd"].
Scientific Foundation
Gut-Brain Axis in Parkinson's Disease
Multiple lines of evidence support a role for the gut in Parkinson's disease pathogenesis:
Enteric nervous system involvement: Alpha-synuclein aggregates appear first in the enteric nervous system and project to the dorsal motor nucleus of the vagus before reaching the substantia nigra, suggesting a prion-like propagation pattern from gut to brain via the vagus nerve[@gut_brain_pd]
Microbiome alterations: Parkinson's disease patients consistently show altered gut microbiome composition compared to healthy controls, with reduced short-chain fatty acid (SCFA)-producing bacteria and increased pro-inflammatory species[@microbiome_alpha_syn]
Intestinal inflammation: Colonic biopsies from Parkinson's disease patients show elevated inflammatory markers, increased permeability, and immune activation[@gut_inflammation_pd]
SCFA deficiency: Short-chain fatty acids (butyrate, propionate, acetate) produced by gut bacteria regulate gut barrier integrity, modulate microglial function, and have neuroprotective properties[@scfa_neuro]. Reduced SCFA production in Parkinson's disease may contribute to both gut and CNS pathology.
Therapeutic Approaches
Riken Seirogan is developing three complementary approaches:
Microbiome Restoration
Fecal microbiota transplantation (FMT) and defined bacterial consortia designed to restore a healthy microbiome composition. This approach targets the root cause of SCFA deficiency and intestinal inflammation[@fecal_transplant_pd].
Postbiotic Metabolites
Purified or engineered SCFA derivatives and other gut-derived metabolites that can be administered orally to restore neuroprotective signaling even when microbiome composition cannot be fully normalized.
Alpha-Synuclein Propagation Inhibition
Compounds that prevent gut bacteria from generating metabolites that promote alpha-synuclein misfolding and propagation.
Pipeline
RS-301 (Lead Program)
Target: Defined bacterial consortium for SCFA restoration
Stage: Preclinical (manufacturing development)
Indication: Parkinson's disease
RS-301 is an oral formulation of 12 bacterial strains selected for their SCFA-producing capacity and ability to colonize the gut. The consortium was identified through analysis of the gut microbiome of healthy Japanese elderly and validated in alpha-synuclein transgenic mouse models, where it reduced alpha-synuclein pathology in the gut and brain[@microbiome_alpha_syn].
RS-302 is a gut-restricted derivative of butyrate designed to provide the neuroprotective benefits of SCFA signaling without systemic exposure. The compound activates GPR109a on gut epithelial and immune cells, reducing intestinal inflammation and indirectly modulating microglial activation.
Connection to NeuroWiki Topics
Riken Seirogan's work intersects with key mechanisms in NeuroWiki: