DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Wilson disease — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleWilson disease maps to a 5-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 wilson disease 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
cytochrome P450 family 11 subfamily A member 1 (CYP11A1) — CYP11A1 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 hemdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3N9Y · 2.1 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
What the evidence adds up to
Fifty patients with Wilson disease underwent MR imaging, CT, abdominal duplex ultrasound, and neurologic examination in a 1996 cross-sectional study. Supratentorial and infratentorial abnormalities in grey and white matter were found in the pyramidal and extrapyramidal system. An abnormal striatum on MR imaging correlated with pseudoparkinsonian signs, an abnormal dentatothalamic tract correlated with cerebellar signs, and an abnormal pontocerebellar tract correlated with pseudoparkinsonian signs. The presence of a portosystemic shunt was strongly associated with abnormality of the globus pallidus. The authors concluded that MR imaging findings were of some use in clinical treatment.
A 2010 questionnaire study of 104 patients with Wilson disease assessed persistence with d-penicillamine and zinc sulphate. The analysis found no difference in persistence between the two drugs or in their reported efficacy. However, regardless of which drug was used, persistence with treatment was associated with significantly better self-assessment: total improvement in 39.7% of the persistent group versus 7.7% in the non-persistent group (p = 0.003); partial improvement in 53.8% versus 30.8% (p = 0.045); and deterioration in none of the persistent group versus 42.3% of the non-persistent group (p < 0.0001). The authors stated that lack of persistence is frequent among patients and that non-compliance decreases the chance of improvement and may cause clinical deterioration.
A 2016 review article notes that Wilson disease is a rare genetic disorder with protean manifestations and should be considered in any patient with unexplained neurologic, psychiatric, or hepatic dysfunction. It states that failure to diagnose and treat Wilson disease results in progressive and ultimately irreversible damage to the neurologic and other systems. A 2011 genetic study of 176 patients with Wilson disease and 414 normal subjects found that a c.1084A>G (p.Thr362Ala) variant in the DCTN4 gene, which interacts with ATP7B, was more prevalent in patients (odds ratio 3.14, 95% confidence interval 1.36–7.22, P = 0.0094). The authors suggest this variant may be associated with the pathogenesis of Wilson disease.
What remains missing is a prospective trial that directly compares d-penicillamine and zinc sulphate with objective, standardised endpoints rather than self-reported well-being. The genetic association in DCTN4 requires replication in independent cohorts before it can inform patient stratification. No study in this set addresses whether any drug can reverse established neurologic damage, and the 2010 data show that even with treatment, only about 40% of persistent patients report total improvement.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Radiology · 1996 · 164 citations
Wilson disease: findings at MR imaging and CT of the brain with clinical correlation.
AbstractPURPOSE: To describe the spectrum of brain abnormalities in Wilson disease (hepatolenticular degeneration) as depicted at magnetic resonance (MR) imaging and computed tomography (CT) and to relate these findings to neurologic and hepatologic abnormalities. MATERIALS AND METHODS: Fifty patients with Wilson disease participated in the cross-sectional study: Patients underwent cerebral MR imaging (n = 49), CT (n = 44), abdominal duplex ultrasound (US) (n = 46), and neurologic examination (n = 50) within a week. Relative risk and the Fisher exact test were used for statistical analysis. RESULTS: Supratentorial and infratentorial abnormalities in the gray and white matter were found in the pyramidal and extrapyramidal system. In Wilson disease, an abnormal striatum depicted on MR images correlated with pseudoparkinsonian signs, an abnormal dentatothalamic tract correlated with cerebellar signs, and an abnormal pontocerebellar tract correlated with pseudoparkinsonian signs. The presence of portosystemic shunt was strongly associated with abnormality of the globus pallidus. CONCLUSION: MR imaging findings were of some use in the clinical treatment of patients with Wilson disease.
Neurologia i Neurochirurgia Polska · 2010 · 62 citations
Persistence with treatment in patients with Wilson disease
AbstractWilson disease is genetically induced failure of copper metabolism. If untreated, it may lead to death within several years from the onset of symptoms. Use of medication should therefore continue over the whole span of the patient's life after the diagnosis. Clinical observations show that patients with Wilson disease frequently stop the treatment. The aim of our study was to assess how drug compliance (defined as persistence with drug use) translates into the total well-being of patients with Wilson disease. Patients diagnosed with Wilson disease and observed in our outpatient clinics were asked to fill in the self-completed questionnaire. Questions were related to demographic data, characteristics of the disease, methods of treatment and persistence with treatment, subjective assessment of health status and treatment efficacy. The EQ-5D questionnaire with a visual analogue scale of well-being was also used. Responses were obtained from 120 subjects but only 104 questionnaires could be further processed. Our analysis did not reveal differences in persistence with d-penicillamine and zinc sulphate use or efficacy of prescribed medication. We found, however, that regardless of the medication used, persistence with treatment resulted in significantly better results of self-assessment (total improvement in 39.7% vs. 7.7% in the non-persistent group, p = 0.003; partial improvement in 53.8% vs. 30.8%, respectively, p = 0.045; and deterioration: none in the persistent group vs. 42.3% in the non-persistent group, p < 0.0001). Lack of persistence with use of prescribed medication is rather frequent among patients with Wilson disease. Lack of compliance decreases chances for improvement and might be the cause of clinical deterioration. Choroba Wilsona jest genetycznie uwarunkowanym zaburzeniem metabolizmu miedzi. U osób nieleczonych może doprowadzić do zgonu w ciągu kilku lat od wystąpienia pierwszych objawów. Stosowanie leków jest zatem długotrwałe i powinno odbywać się przez całe dalsze życie chorego. Obserwacje kliniczne pokazują, że pacjenci z chorobą Wilsona często przerywają terapię. Celem naszego badania była ocena, w jaki sposób przestrzeganie zaleceń lekarza odnoszących się do farmakoterapii (definiowane głównie jako wytrwałość w przyjmowaniu leku) przekłada się na stan pacjentów z chorobą Wilsona. Wśród chorych na chorobę Wilsona leczonych w naszej poradni przeprowadzono badanie ankietowe. Pacjenci samodzielnie wypełniali kwestionariusz zawierający pytania o dane demograficzne, charakterystykę choroby, sposób leczenia, wytrwałość w leczeniu, subiektywną ocenę stanu zdrowia i skuteczności terapii. Wykorzystano również kwestionariusz EQ-5D ze wzrokową skalą oceny samopoczucia. W badaniu wzięło udział 120 chorych, ale tylko 104 kwestionariusze nadawały się do oceny. Przeprowadzona analiza nie wykazała różnic w wytrwałości przyjmowania d-penicylaminy oraz soli cynku ani różnic w skuteczności obu leków. Stwierdzono jednak, że niezależnie od przyjmowanego leku, wytrwałość w jego stosowaniu wiąże się ze znacząco lepszą samodzielną oceną stanu zdrowia w badaniu kwestionariuszowym (pełna poprawa nastąpiła u 39,7% przyjmujących leki bez dłuższych przerw wobec 7,7% w grupie niestosującej się do zaleceń lekarza, p = 0,003; częściowa poprawa odpowiednio u 53,8% i 30,8%, p = 0,045, a pogorszenie nie miało miejsca u żadnego z chorych przyjmujących lek wobec 42,3% w grupie, która nie przyjmowała leku stale, p <0,0001). Brak wytrwałości w leczeniu występuje dość często wśród pacjentów z chorobą Wilsona. Niestosowanie się do zaleceń dotyczących przyjmowania leków zmniejsza szansę na wystąpienie poprawy i może być przyczyną pogorszenia stanu klinicznego.
CONTINUUM Lifelong Learning in Neurology · 2016 · 34 citations
Wilson Disease
AbstractPURPOSE OF REVIEW: This article reviews the clinical features of Wilson disease, focusing on the neurologic and psychiatric abnormalities, and addresses the diagnostic workup and treatment approaches to managing the disease. RECENT FINDINGS: The list of known mutations causing Wilson disease continues to grow, but advances in genetic testing may soon make it feasible to routinely perform genetic testing on individuals suspected of having Wilson disease. SUMMARY: Wilson disease is a rare genetic disorder with protean manifestations that should be considered in the differential diagnosis of any individual presenting with unexplained neurologic, psychiatric, or hepatic dysfunction. Appropriate diagnostic testing should be expeditiously performed and treatment promptly initiated and maintained since failure to diagnose and treat Wilson disease will result in progressive and ultimately irreversible damage to the neurologic and other systems.
Association of a c.1084A&gt;G (p.Thr362Ala)Variant in the DCTN4 Gene with Wilson Disease
AbstractMaterials and Methods: The sequence of the coding regions and exon-intron boundaries of the five ATP7B-interacting genes, ATOX1, COMMD1, GLRX, DCTN4, and ZBTB16, were analyzed in the 12 patients with Wilson disease. Results: Three nonsynonymous variants including c.1084A>G (p.Thr362Ala) in the exon 12 of the DCTN4 gene were identified in the patients examined. Among these, only p.Thr362Ala was predicted as possibly damaging protein function by in silico analysis. Examination of allele frequency of c.1084A>G (p.Thr362Ala) variant in the 176 patients with Wilson disease and in the 414 normal subjects revealed that the variant was more prevalent in the Wilson disease patients (odds ratio [OR]=3.14, 95% confidence interval=1.36-7.22, P =0.0094). Conclusion: Our result suggests that c.1084A>G (p.Thr362Ala) in the ATP7B-interacting DCTN4 gene may be associated with the pathogenesis of Wilson disease.
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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