DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tuberous sclerosis 1 — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTuberous sclerosis 1 maps to a 4-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
approvedMelatoninMelatonin receptor agonist
Structures already discussed alongside tuberous sclerosis 1 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of fad quinone reductase 2 — Melatonin has a real, experimentally solved structure in complex with this target (PDB 4QOG, 1.4 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet ml1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4QOG · 1.4 Å · ligand Melatonin (ML1). Experimental structure, not a prediction.
What the evidence adds up to
In a 1999 randomised double-blind placebo-controlled crossover trial of melatonin for severe sleep problems in tuberous sclerosis, seven patients were enrolled. Melatonin produced a small but clinically significant improvement in total sleep time, a mean gain of 0.55 hours (P<0.05). Sleep-onset time tended to improve but did not reach statistical significance. Melatonin had no discernible effect on the number of night-time awakenings. The authors concluded that melatonin prolongs total sleep time in this population and called for further trials on dosage, tolerance, and drug interactions.
Pulmonary involvement in tuberous sclerosis is rare and occurs almost exclusively in women of child-bearing age, presenting as spontaneous pneumothorax or progressive dyspnoea. A 2004 case report describes a 4-year-old boy with tuberous sclerosis diagnosed in infancy who had predominantly respiratory symptoms, frequently meeting acute respiratory distress syndrome criteria, with pathologically confirmed lung involvement. This case is exceptional because of the patient’s young age and male sex.
A 2014 case report describes a 19-year-old woman with tuberous sclerosis and multiple bilateral renal angiomyolipomas, the largest measuring 6 cm. She was treated first with a low dose of the mTOR inhibitor sirolimus (up to 3 mg/day for 12 months). After significant reduction in angiomyolipoma size, percutaneous cryoablation was performed. No side-effects from either treatment were reported. At 12 months after cryoablation, no recurrence of the angiomyolipoma was noted. This is the first report of this combined strategy; the authors present it as a novel tool but caution that it is a single case.
A retrospective study of 67 patients with tuberous sclerosis seen in Spanish dermatology clinics between 1994 and 2007 found that all patients had neurological or dermatological disorders. Other disorders, in descending frequency, were psychiatric (55.5%), renal (32.8%), cardiac (22.4%), skeletal and pulmonary (13.4%), and ophthalmological (11.9%). The authors state that these findings support previously published data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Developmental Medicine & Child Neurology · 1999 · 30 citations
Use of melatonin to treat sleep disorders in tuberous sclerosis
AbstractThe results of a therapeutic trial of the use of melatonin in patients with tuberous sclerosis complex who also have severe sleep problems are reported. We used a randomized double‐blind placebo‐controlled crossover design. Seven patients with confirmed diagnoses of tuberous sclerosis and significant sleep disorder were recruited. We employed three outcome measures: total sleep time, time to sleep onset, and number of awakenings. Patients treated with melatonin had a small but clinically significant improvement in total sleep time (mean improvement 0.55 hours, P<0.05). They also tended to have an improvement in sleep‐onset time but this did not reach statistical significance. Melatonin, in this trial, had no discernible effect on sleep fragmentation. We conclude that melatonin does have a beneficial effect in prolonging the total sleep time of patients with tuberous sclerosis and sleep disorder and that further trials are necessary to investigate the issues of optimal dosage, tolerance, and possible interactions with other medications.
AbstractTuberous sclerosis is a neurocutaneous syndrome involving many tissues. Pulmonary involvement is rare. Pulmonary cases are usually women of child-bearing age who present with spontaneous pneumothorax or progressive dyspnea. In childhood and, even more, in male patients, pulmonary involvement by tuberous sclerosis is exceptional. We report on a 4-year-old male patient diagnosed in the first months of life with tuberous sclerosis with predominantly respiratory symptoms (frequently with acute RDS criteria), in whom lung involvement was pathologically confirmed.
Percutaneous cryoablation for tuberous sclerosis-associated renal angiomyolipoma with neoadjuvant mTOR inhibition
AbstractBACKGROUND: Renal angiomyolipomas (AMLs) are frequent in tuberous sclerosis and are responsible for a significant proportion of the morbidity in adulthood, mainly from bleeding complications, which are correlated to the size of the AMLs. We describe the case of a 19-year-old female with multiple bilateral renal angiomyolipomas. CASE PRESENTATION: The renal AMLs measured up to 6 cm in size. She was first treated with a low dose of the mammalian target of rapamycin (mTOR) inhibitor sirolimus (up to 3 mg/day over a 12-month period) and following significant AML size reduction, percutaneous cryoablation was performed. No side-effects of either treatment were reported. At 12 months post-cryoablation, no recurrence of the AML was noted. CONCLUSION: This is the first report of this treatment strategy and the case study reveals that combining a low dose of an mTOR inhibitor with percutaneous cryoablation to treat small tumors mitigates the side-effects while providing a good clinical outcome. This therapeutic approach is a novel tool for the clinician involved in the management of patients with tuberous sclerosis.
Actas Dermo-Sifiliográficas · 2009 · 3 citations · open access
Clinical Findings in 67 Patients With Tuberous Sclerosis
AbstractTuberous sclerosis is an uncommon neurocutaneous syndrome characterized by the appearance of hamartomas in multiple organs. Diagnosis is based on clinical criteria. To report the clinical findings in a series of 67 patients with tuberous sclerosis. This was a descriptive and observational retrospective study of patients with tuberous sclerosis referred to our dermatology clinics between January 1994 and March 2007. All patients presented neurological or dermatological disorders. Other disorders, in descending frequency, were psychiatric (55.5%), renal (32.8%), cardiac (22.4%), skeletal and pulmonary (13.4%), and ophthalmological (11.9%). We report the clinical findings in a series of patients with tuberous sclerosis. According to our literature search, this is the first such study in the Spanish population. Overall, our findings support those already published. La esclerosis tuberosa (ET) es un síndrome neurocutáneo infrecuente caracterizado por la aparición de hamartomas en múltiples órganos. Su diagnóstico se basa en criterios clínicos. Describir los hallazgos clínicos en una serie de 67 pacientes afectos de ET. Llevamos a cabo un estudio retrospectivo, descriptivo y observacional de los pacientes con ET remitidos a nuestras consultas de Dermatología entre enero de 1994 y marzo de 2007. El 100% de los pacientes presentaron alteraciones neurológicas o dermatológicas. El resto fueron, por orden: psiquiátricas (55,5%), renales (32,8%), cardíacas (22,4%), esqueléticas y pulmonares (13,4%) y oftalmológicas (11,9%). Describimos los hallazgos clínicos en una serie de pacientes afectos de ET. Se trata, según la literatura revisada, del primer estudio de este tipo en la población española. Globalmente, nuestros datos apoyan lo hasta ahora publicado.
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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