Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMJ42E6)

• Drug Name: ProSavin Drug Info
• Synonyms: Dopamine synthesis pathway gene therapy (Parkinson's disease), Oxford BioMedica

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Phase 1/2	[1]

• Cross-matching ID: TTD Drug ID: DMJ42E6

Molecule-Related Drug Atlas

Drug(s) Targeting GTP cyclohydrolase-I (GCH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Guanine	DMIWLJE	N. A.	N. A.	Phase 3	[3]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[4]
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[5]
Guanosine-5'-Triphosphate	DMV2OJX	Discovery agent	N.A.	Investigative	[6]
8-hydroxyguanine	DMT9BPN	Discovery agent	N.A.	Investigative	[3]

Drug(s) Targeting Aromatic-L-amino-acid decarboxylase (DDC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin B6	DMDBZMV	Vitamin B6 deficiency	5B5D	Approved	[7]
Carbidopa	DMHRG8Q	Parkinson disease	8A00.0	Approved	[8]
Patrome	DM3H2U4	Parkinson disease	8A00.0	Phase 3	[9]
Benserazide	DMLU8NX	N. A.	N. A.	Phase 3	[8]
AV-201	DMDL9WU	Parkinson disease	8A00.0	Phase 2	[10]
VY-AADC	DMPSBTL	Parkinson disease	8A00.0	Phase 2	[11]
GT-AADC	DM8N3OQ	Aromatic L-amino acid decarboxylase deficiency	5C59.00	Phase 2	[12]
PTC-AADC	DM9ZHE3	Aromatic L-amino acid decarboxylase deficiency	5C59.00	Phase 2	[13]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[4]
VY-AADC01	DM0N71R	Parkinson disease	8A00.0	Phase 1	[14]

Drug(s) Targeting Tyrosine 3-monooxygenase (TH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Phenylalanine	DMQXI9F	Malnutrition	5B50-5B71	Approved	[15]
L-Tyrosine	DM9O8DT	Malnutrition	5B50-5B71	Approved	[16]
Tetrahydrobiopterin	DMINZ4W	Malnutrition	5B50-5B71	Approved	[17]
Metyrosine	DMBYCU0	Pheochromocytoma	5A75	Approved	[18]
L1-79	DMLHPVW	Autism spectrum disorder	6A02	Phase 2	[19]
OXB-102	DMXF9DM	Parkinson disease	8A00.0	Phase 1/2	[4]
7,8-dihydrobiopterin	DMQU4XM	Discovery agent	N.A.	Investigative	[6]
alpha-propyldopacetamide	DMQKMX3	Discovery agent	N.A.	Investigative	[20]
Meta-Tyrosine	DM0748C	Discovery agent	N.A.	Investigative	[6]
3-iodotyrosine	DMNZMH6	Discovery agent	N.A.	Investigative	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aromatic-L-amino-acid decarboxylase (DDC)	TTN451K	DDC_HUMAN	Modulator	[2]
GTP cyclohydrolase-I (GCH1)	TTLSWP6	GCH1_HUMAN	Modulator	[2]
Tyrosine 3-monooxygenase (TH)	TTUHP71	TY3H_HUMAN	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT01856439) Long Term Safety and Efficacy Study of ProSavin in Parkinson's Disease. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [3] GTP cyclohydrolase I feedback regulatory protein-dependent and -independent inhibitors of GTP cyclohydrolase I. Arch Biochem Biophys. 2001 Apr 1;388(1):67-73.
• [4] Clinical pipeline report, company report or official report of Oxford BioMedica.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] Functional COMT variant predicts response to high dose pyridoxine in Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet. 2005 Aug 5;137B(1):1-4.
• [8] Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease. Semin Neurol. 2001;21(1):15-22.
• [9] The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin Cancer Res. 2000 Nov;6(11):4365-72.
• [10] UCSF report
• [11] Clinical pipeline report, company report or official report of Voyager Therapeutics.
• [12] Clinical pipeline report, company report or official report of PTC Therapeutics.
• [13] ClinicalTrials.gov (NCT04903288) An Open-Label Trial to Address the Safety of the SmartFlow MR-Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Subjects. U.S.National Institutes of Health.
• [14] Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial. Neurology. 2022 Jan 4;98(1):e40-e50.
• [15] Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. Curr Med Chem. 2007;14(4):455-67.
• [16] Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: comparison with that on tyrosine hydroxylase activity. Neurosci Lett. 2006 Jul 3;401(3):261-5.
• [17] Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. J Neural Transm Suppl. 2007;(72):113-20.
• [18] Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension. 1991 Jul;18(1):1-8.
• [19] Effect of L1-79 on Core Symptoms of Autism Spectrum Disorder: A Case Series. Clin Ther. 2019 Oct;41(10):1972-1981.
• [20] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1243).