DeCure for SLC6A3-related dopamine transporter deficiency syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for SLC6A3-related dopamine transporter deficiency syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSLC6A3-related dopamine transporter deficiency syndrome maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for slc6a3-related dopamine transporter deficiency syndrome is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
solute carrier family 6 member 3 (SLC6A3) — SLC6A3 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet clrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9EO4 · 2.66 Å · ligand CHOLESTEROL (CLR). Experimental structure, not a prediction.
What the evidence adds up to
In 30 healthy subjects, those homozygous for the 10-repeat allele at the SLC6A3 3' VNTR polymorphism showed significantly lower dopamine transporter binding than carriers of the nine-repeat allele, as measured by SPECT with [123I]beta-CIT. No effect of SLC6A4 genotype on serotonin transporter binding was observed. The authors concluded that genetic variation at this polymorphism may modify dopamine transporter function.
A review from 2017 summarises that the dopamine transporter, encoded by SLC6A3, controls both extracellular and intracellular dopamine concentrations, and that unbalanced dopamine levels are involved in numerous mental disorders. The review discusses animal models, neuropsychology, and neuroimaging investigations but does not report any new experimental data or clinical trial results.
In 2,364 participants from the PLCO Cancer Screening Trial, four SLC6A3 polymorphisms were genotyped. Compared with individuals of normal BMI, obese individuals at baseline were less likely to carry the 3' VNTR 9-repeat allele in a dose-dependent manner (OR for *9 = 0.80, OR for 99 = 0.47, Ptrend = 0.005). At age 50, overweight individuals (OR = 0.80, 95% CI 0.65–0.99, p = 0.04) and obese individuals (OR = 0.70, 95% CI 0.49–0.99, p = 0.04) were less likely to carry the A-C-G-9 haplotype. The authors concluded that genetic variation at SLC6A3 may modify BMI.
No abstract in this set describes any therapeutic intervention, drug repurposing trial, or clinical outcome for SLC6A3-related dopamine transporter deficiency syndrome. What remains missing is any direct evidence linking these genetic associations to a specific drug response, any prospective trial testing a repurposed agent in patients with confirmed SLC6A3 mutations, and any stratification of patients by genotype or transporter binding status.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Psychiatry · 2000 · 276 citations
Prediction of Dopamine Transporter Binding Availability by Genotype: A Preliminary Report
AbstractOBJECTIVE: Evidence of a relationship between genotype and binding availability was assessed for the dopamine and serotonin transporter genes. METHOD: The authors assessed dopamine transporter genotype at the SLC6A3 3' variable number of tandem repeats (VNTR) polymorphism and serotonin transporter genotype at the SLC6A4 promotor VNTR polymorphism in 30 healthy subjects who also underwent single photon emission computed tomography with [(123)I]beta-CIT. RESULTS: Subjects homozygous for the 10-repeat allele at the SLC6A3 locus demonstrated significantly lower dopamine transporter binding than carriers of the nine-repeat allele. There was no effect of SLC6A4 genotype upon serotonin transporter binding. CONCLUSIONS: These findings suggest that genetic variation at the SLC6A3 3' VNTR polymorphism may modify dopamine transporter function.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics · 2017 · 81 citations · open access
The dopamine transporter role in psychiatric phenotypes
AbstractThe dopamine transporter (DAT) is one of the most relevant and investigated neurotransmitter transporters. DAT is a plasma membrane protein which plays a homeostatic role, controlling both extracellular and intracellular concentrations of dopamine (DA). Since unbalanced DA levels are known to be involved in numerous mental disorders, a wealth of investigations has provided valuable insights concerning DAT role into normal brain functioning and pathological processes. Briefly, this extensive but non-systematic review discusses what is recently known about the role of SLC6A3 gene which encodes the dopamine transporter in psychiatric phenotypes. DAT protein, SLC6A3 gene, animal models, neuropsychology, and neuroimaging investigations are also concisely discussed. To conclude, current challenges are reviewed in order to provide perspectives for future studies.
BMC Medical Genetics · 2009 · 15 citations · open access
SLC6A3and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
AbstractBACKGROUND: To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. METHODS: Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5-24.9, 25.0-29.9, or > or = 30 kg/m2, respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression. RESULTS: Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR*9 = 0.80, OR99 = 0.47, Ptrend = 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; ORA-C-G-9 = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A-C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9). CONCLUSION: Our results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
