Version history

{
  "description": "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.",
  "target_gene": "TH, AADC",
  "target_pathway": "Tyrosine hydroxylase / catecholamine synthesis",
  "disease": "neurodegeneration",
  "hypothesis_type": "mechanistic",
  "status": "archived",
  "confidence_score": 0.2,
  "novelty_score": 0.9,
  "feasibility_score": 0.1,
  "impact_score": 0.4,
  "composite_score": 0.384,
  "mechanistic_plausibility_score": 0.3,
  "druggability_score": 0.2,
  "safety_profile_score": 0.2,
  "evidence_for": [
    {
      "doi": "10.1002/jimd.12791",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39166734/",
      "pmid": "39166734",
      "year": "2025",
      "claim": "Mild/moderate phenotypes in AADC deficiency: Focus on the aromatic amino acid decarboxylase protein.",
      "caveat": "Search-derived citation; verify claim-level fit before promotion.",
      "source": "J Inherit Metab Dis",
      "strength": "medium"
    },
    {
      "doi": "10.3390/ijms231911238",
      "url": "https://pubmed.ncbi.nlm.nih.gov/36232540/",
      "pmid": "36232540",
      "year": "2022",
      "claim": "Compound Heterozygosis in AADC Deficiency and Its Complex Phenotype in Terms of AADC Protein Population.",
      "caveat": "Search-derived citation; verify claim-level fit before promotion.",
      "source": "Int J Mol Sci",
      "strength": "medium"
    },
    {
      "doi": "10.1038/s41467-021-24524-8",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34253733/",
      "pmid": "34253733",
      "year": "2021",
      "claim": "Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons.",
      "caveat": "Search-derived citation; verify claim-level fit before promotion.",
      "source": "Nat Commun",
      "strength": "medium"
    },
    {
      "doi": "10.1002/ajmg.c.31670",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30614627/",
      "pmid": "30614627",
      "year": "2019",
      "claim": "A review of aromatic l-amino acid decarboxylase (AADC) deficiency in Taiwan.",
      "caveat": "Search-derived citation; verify claim-level fit before promotion.",
      "source": "Am J Med Genet C Semin Med Genet",
      "strength": "medium"
    },
    {
      "doi": "10.1016/j.ymgmr.2021.100762",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33996491/",
      "pmid": "33996491",
      "year": "2021",
      "claim": "Blood, urine and cerebrospinal fluid analysis in TH and AADC deficiency and the effect of treatment.",
      "caveat": "Search-derived citation; verify claim-level fit before promotion.",
      "source": "Mol Genet Metab Rep",
      "strength": "medium"
    }
  ],
  "evidence_against": [
    {
      "url": "https://pubmed.ncbi.nlm.nih.gov/31196984/",
      "pmid": "31196984",
      "year": "2019",
      "claim": "Gut bacteria can metabolize levodopa through an interspecies pathway, implying engineered gut catecholamine precursor production may be degraded or pharmacokinetically unstable.",
      "title": "Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.",
      "caveat": "Counter-evidence curated for task 9df1f940-93f3-4f2f-9a72-89e8f93d2276; verify claim-level fit before promotion.",
      "source": "Science",
      "strength": "medium",
      "evidence_type": "counter_evidence"
    },
    {
      "url": "https://pubmed.ncbi.nlm.nih.gov/30659181/",
      "pmid": "30659181",
      "year": "2019",
      "claim": "Gut bacterial tyrosine decarboxylases restrict levodopa levels, directly challenging assumptions that intestinal bacterial dopamine-precursor handling is reliably beneficial.",
      "title": "Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease.",
      "caveat": "Counter-evidence curated for task 9df1f940-93f3-4f2f-9a72-89e8f93d2276; verify claim-level fit before promotion.",
      "source": "Nat Commun",
      "strength": "medium",
      "evidence_type": "counter_evidence"
    }
  ],
  "market_price": 0.4108
}