Our Science
Integrated Precision Medicine Based on PARIS(ZNF746)
YEPBIO is a neurodegeneration-focused biotech developing an integrated precision medicine approach for Parkinson's disease, combining disease-modifying therapeutics (DMTs) with blood-based early diagnostic biomarkers and diagnostic kits. Backed by the scientific ownership of our team — which first discovered and characterized PARIS (ZNF746) — we have established PARIS as a top-tier pathogenic axis across both genetic and sporadic PD. Our lead asset, YPD-01, is the world's first oral first-in-class small-molecule candidate designed to directly target PARIS.
PARIS(ZNF746) — The Central Hub Target of Parkinson's Disease
PARIS (Parkin Interacting Substrate, ZNF746) is a transcriptional regulator degraded through Parkin-mediated ubiquitination. When Parkin function is impaired, PARIS accumulates abnormally as a genetic driver of Parkinson's disease. Accumulated PARIS suppresses PGC-1α, a key regulator of mitochondrial biogenesis, leading to mitochondrial dysfunction and dopaminergic neuronal death.
Genetic & Pathological Evidence
PARIS mRNA expression in peripheral blood of PD patients was approximately 2-fold higher than controls (PD 2.33 vs. control 1.07). In a cohort of 743 early-onset PD patients, 11 PARIS(ZNF746) variants were identified, and PARIS variants were confirmed in 12 out of 100 PD patients. Various PD causative factors — Parkin loss, PINK1 loss, c-Abl activation, α-synuclein PFF, GBA mutation, and neuroinflammation — all converge on PARIS accumulation.
Disease-Modifying Therapy Target
PARIS is recognized as a next-generation key drug target by the Michael J. Fox Foundation (MJFF), Cure Parkinson's, Johns Hopkins University, and other leading global research groups. MJFF has explicitly designated PARIS as a core target in its preclinical therapeutics pipeline.
Precision Medicine — PARIS-PD Subtype Classification
Through PARIS genetic variants and blood-based biomarkers (PARIS antigen and autoantibody), we select PARIS-High patient subgroups and apply YPD-01 precision disease-modifying therapy (DMT). The dual biomarker (PARIS Ag + autoAb) diagnostic achieves 91.6% sensitivity and 87.5% specificity, enabling precise selection of PARIS-PD subtype patients comprising approximately 10-20% of PD patients.
YPD-01 — World's First Small-Molecule Therapy Designed to Inhibit PARIS
Patent number 10-2186761
YPD-01 restores PGC-1α signaling and supports mitochondrial resilience in dopaminergic neurons, designed to halt the disease process in Parkinson's disease.
Restores PGC-1α signaling
Restores PGC-1α expression in key brain regions
Protects dopaminergic neurons
Protects dopaminergic neurons across multiple PD models
Improves motor function
Demonstrated motor function improvement in animal models
Robust PK · BBB · safety
Shows a robust pharmacokinetic, BBB, and safety profile
PARIS-PGC-1α-Mitochondria Axis
Dopaminergic Neuronal Death Pathway
Landmark Paper — Discovery of PARIS
The seminal work in which YEPBIO CTO Jooho Shin first identified PARIS (ZNF746) at Ted Dawson's lab, Johns Hopkins University. It established the core mechanism by which PARIS represses PGC-1α and drives dopaminergic neurodegeneration, and has been cited over 1,100 times — laying the foundation for PARIS-targeted drug development.
PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson's Disease
Shin JH, Ko HS, Kang H, Lee Y, Lee YI, Pletinkova O, Troconso JC, Dawson VL, Dawson TM
DOI: 10.1016/j.cell.2011.02.010
Key Follow-Up Studies
Major follow-up studies that expanded the PARIS research
PARIS farnesylation prevents neurodegeneration in models of Parkinson's disease
Jo A, Lee Y, Stevens DA, et al.
Proximity proteomic analysis of the NRF family reveals the Parkinson's disease protein ZNF746/PARIS as a co-complexed repressor of NRF2
LaPak K, et al.
Preclinical studies and transcriptome analysis in a model of Parkinson's disease with dopaminergic ZNF746 expression
Kim S, et al.
Genetic variants of ZNF746 and the level of plasma Parkin, PINK1, and ZNF746 proteins in patients with Parkinson's disease
Dorszewska J, et al.
PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival
Lee Y, Stevens DA, Kang SU, et al.
Parkin interacting substrate phosphorylation by c-Abl drives dopaminergic neurodegeneration
Kim H, Shin JY, Jo A, et al.
Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration
Stevens DA, Lee Y, Kang SU, et al.
Parkin interacting substrate zinc finger protein 746 is a pathological mediator in Parkinson's disease
Brahmachari S, et al.
Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease
Panicker N, et al.