DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for AMED syndrome, digenic — 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 moduleAMED syndrome, digenic 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 amed syndrome, digenic 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
aldehyde dehydrogenase 2 family member (ALDH2) — ALDH2 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 gaidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5L13 · 2.4 Å · ligand GUANIDINE (GAI). Experimental structure, not a prediction.
What the evidence adds up to
The three abstracts provided do not concern AMED syndrome. The first describes ixekizumab versus adalimumab in psoriatic arthritis. The second reports decitabine combined with modified CAG for relapsed or refractory acute myeloid leukaemia with AML1-ETO. The third describes a case of digenic Alport syndrome caused by variants in COL4A4 and COL4A5. No abstract mentions AMED syndrome, its digenic basis, or any drug tested in that disease.
For AMED syndrome, no clinical trial data, no case series, and no preclinical drug-repurposing evidence are available in these abstracts. The natural history, molecular mechanism, and any candidate interventions for AMED syndrome remain unaddressed by the studies provided.
What is missing is any dedicated funding for AMED syndrome research, any in vitro or animal model work to identify repurposable compounds, and any clinical trial design that could test a candidate drug in the small number of affected patients. Without patient stratification by specific digenic genotype, even a well-funded trial would struggle to detect a signal.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Rheumatology and Therapy · 2020 · 44 citations · open access
Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study
AbstractINTRODUCTION: In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. METHODS: In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher's exact test. Missing data were imputed using non-responder imputation. RESULTS: By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. CONCLUSION: In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.
[Clinical Efficacy of Decitabine Combined with Modified CAG Regimen for Relapse/Refractory Acute Myeloid Leukemia with AML1-ETO<sup></sup>].
AbstractOBJECTIVE: , and therapeutic effcacy and side effects of decitabine combined with modified CAG regimen. METHODS: from June 2015 to January 2016 were analyzed retrospectively, including age, sex, initial symptoms, peripheral blood and bone marrow characteristics and so on. at the same time, the therapeutic effcacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 8 patient were with median age of 44.5(16-59) years. RESULTS: /L, median hemoglobin 1evel was 107(79-131) g/L, median lactate dehydrogenase level was 313.5(124.1-865.9) U/L at the initial diagnosis. The results showed that after treatment with decitabine combined with modified CAG, 7 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 87.5%(7/8). The main side effects of this regimen was myelosupp-ression, there were no new lung infection and other serious complications, 1 case without complete remission was treated with FLAG, and died of heart failure. CONCLUSION: displays higer remission rate and lower side effects.
Case Reports in Nephrology and Dialysis · 2024 · 0 citations · open access
Novel Digenic Variants in <i>COL4A4</i> and <i>COL4A5</i> Causing X-Linked Alport Syndrome: A Case Report
Abstract<b><i>Introduction:</i></b> Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in <i>COL4A4</i> (c.827G&gt;C, p.Gly276Ala) and <i>COL4A5</i> (c.4369G&gt;C, p.Gly1457Arg). <b><i>Case Presentation:</i></b> The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in <i>COL4A4</i> (c.827G&gt;C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in <i>COL4A5</i> (c.4369G&gt;C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. <b><i>Conclusion:</i></b> The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.
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.
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