Engineered probiotic bacteria expressing tyrosine hydroxylase and aromatic L-amino acid decarboxylase could produce L-DOPA locally in the gut, providing sustained dopamine precursor delivery while bypassing hepatic metabolism and reducing motor fluctuations.
Curated pathway from expert analysis
graph TD
A["L-Tyrosine<br/>Substrate"] --> B["Tyrosine Hydroxylase<br/>(TH)"]
C["Tetrahydrobiopterin<br/>(BH4)"] --> B
D["O2 and Fe2+<br/>Cofactors"] --> B
B --> E["L-DOPA<br/>Intermediate"]
E --> F["Aromatic L-amino acid<br/>Decarboxylase (AADC)"]
G["Pyridoxal 5'-phosphate<br/>(PLP)"] --> F
F --> H["Dopamine<br/>Product"]
I["GTP Cyclohydrolase I<br/>(GTPCH1)"] --> J["BH4 Biosynthesis<br/>Pathway"]
K["6-pyruvoyl-tetrahydropterin<br/>Synthase (PTPS)"] --> J
J --> C
L["Engineered Probiotic<br/>Bacteria"] --> B
L --> F
L --> I
L --> K
H --> M["Striatal Dopamine<br/>Restoration"]
M --> N["Improved Motor<br/>Function"]
O["Neurodegeneration<br/>Process"] --> P["Dopamine Depletion"]
P --> Q["Motor Dysfunction<br/>Symptoms"]
classDef normal fill:#4fc3f7,color:#0d0d1a
classDef therapeutic fill:#81c784,color:#0d0d1a
classDef pathology fill:#ef5350,color:#0d0d1a
classDef outcome fill:#ffd54f,color:#0d0d1a
classDef molecular fill:#ce93d8,color:#0d0d1a
class A,C,D,G normal
class B,F,I,J,K,L therapeutic
class O,P,Q pathology
class M,N outcome
class E,H molecular





No curated PDB or AlphaFold mapping for TH yet. Search RCSB →
Median TPM across 13 brain regions for TH, AADC from GTEx v10.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for TH, AADC.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If hypothesis is true, intervention prioritize patients with demonstrated L-DOPA responsiveness but emerging motor fluctuations, as this population represents the optimal risk-benefit profile for init | prioritize patients with demonstrated L-DOPA responsiveness but emerging motor fluctuations, as this population represents the optimal risk-benefit profile for | — no observation — | pending | 0.20 |
| If hypothesis is true, intervention effectively restore dopaminergic signaling in 6-OHDA-treated neuronal cultures, with 70-80% recovery of tyrosine hydroxylase-positive cell populations | effectively restore dopaminergic signaling in 6-OHDA-treated neuronal cultures, with 70-80% recovery of tyrosine hydroxylase-positive cell populations | — no observation — | pending | 0.20 |
| If hypothesis is true, intervention inhibit bacterial growth through feedback mechanisms | inhibit bacterial growth through feedback mechanisms | — no observation — | pending | 0.20 |