DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for infantile spasms — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInfantile spasms maps to a 43-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 infantile spasms 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
neurotrophic receptor tyrosine kinase 2 (NTRK2) — NTRK2 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 4-methoxybenzyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AT5 · 1.71 Å · ligand 5-{3-methoxy-4-[(4-methoxybenzyl)oxy]benzyl}pyrimidine-2,4-diamine (MUJ). Experimental structure, not a prediction.
What the evidence adds up to
In a rat model of cryptogenic infantile spasms, prenatal betamethasone priming followed by postnatal NMDA triggers spasms earlier and in greater numbers than in controls, with clustering, ictal EEG electrodecrements, and interictal large-amplitude waves resembling hypsarrhythmia. Chronic ACTH and methylprednisolone pretreatment suppressed spasm numbers; vigabatrin pretreatment also suppressed spasms, but rapamycin did not. Multiple spasm bouts produced behavioural changes in open field and elevated plus maze tests. The model is offered as a tool for searching for novel treatments.
In a prospective multicentre study of 395 infants with new-onset infantile spasms treated with standard therapy (ACTH, oral steroids, or vigabatrin), 43% (171) achieved clinical remission within the first two weeks. Of those, 81% (138 of 171) responded within the first week. Median time to response was 4 days for ACTH (IQR 3–7), 3 days for oral steroids (IQR 2–5), and 3 days for vigabatrin (IQR 1–6). Infants without hypsarrhythmia on pretreatment EEG were more likely to respond early (hazard ratio 2.23, 95% CI 1.39–3.57). No other clinical factors predicted early response. The authors conclude that children who do not respond within one week should be reassessed immediately for additional standard treatment.
The 2010 chapter notes that the neurobiologic basis of infantile spasms has long been debated with little resolution, and that the recent development of several animal models should provide a paradigm shift. The 1997 book reference is a monograph summarising advances in understanding up to that time.
What remains missing is a clear biological mechanism that can be targeted in humans, a prospective trial comparing early sequential therapy against continued monotherapy in non-responders, and patient stratification beyond the absence of hypsarrhythmia. The rat model has not yet yielded a drug that outperforms ACTH, vigabatrin, or steroids in children.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Epilepsia · 2011 · 82 citations · open access
Validation of the rat model of cryptogenic infantile spasms
AbstractPURPOSE: To determine whether a new model of cryptogenic infantile spasms consisting of prenatal priming with betamethasone and postnatal trigger of spasms by N-methyl-D-aspartate (NMDA) responds to chronic adrenocorticotropic hormone (ACTH) treatment, and has electroencephalography (EEG) signature, efficacy of treatments, and behavioral impairments similar to those in human infantile spasms. METHODS: Rats prenatally primed with betamethasone on gestational day 15 were used. Spasms were triggered with NMDA between postnatal days (P) 10 and 15 in a single session or in multiple sessions in one subject. The expression of spasms was compared to prenatally saline-injected controls. Effects of relevant treatments (ACTH, vigabatrin, methylprednisolone, rapamycin) were determined in betamethasone-primed rats. In the rats after spasms, behavioral evaluation was performed in the open field and elevated plus maze on P20-22. KEY FINDINGS: NMDA at P10-15 (the rat "infant" period) triggers the spasms significantly earlier and in greater numbers in the prenatal betamethasone-exposed brain compared to controls. Similar to human condition, the spasms occur in clusters. Repeated trigger of spasms is associated with ictal EEG electrodecrements and interictal large-amplitude waves, a possible rat variant of hypsarrhythmia. Chronic ACTH treatment in a randomized experiment, and chronic pretreatment with methylprednisolone significantly suppress the number of spasms similar to the human condition. Pretreatment with vigabatrin, but not rapamycin, suppressed the spasms. Significant behavioral changes occurred following multiple bouts of spasms. SIGNIFICANCE: The model of infantile spasms has remarkable similarities with the human condition in semiology, EEG, pharmacologic response, and long-term outcome. Therefore, the model can be used to search for novel and more effective treatments for infantile spasms.
Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms
AbstractBACKGROUND AND OBJECTIVES: Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response. METHODS: The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new-onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (ACTH, oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks after treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response. RESULTS: Among 395 infants, clinical infantile spasms remission occurred in 43% (n = 171) within the first 2 weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range [IQR] 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pretreatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% CI 1.39-3.57). No other clinical factors predicted early responders to therapy. DISCUSSION: Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.
AbstractSummary The neurobiologic basis for infantile spasms has long been debated but with little resolution. The very recent development of several animal models of this disorder should provide a paradigm shift in our understanding of this disorder. This chapter outlines unresolved questions and suggests experimental approaches to answering them. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books ).
Abstractedited by Olivier Dulac, Harry T. Chugani, and Bernardo Dalla Bernardina, 310 pp., ill., London, W.B. Saunders Company, Ltd., 1994, $82.00.
It has been a long time since a comprehensive monograph about infantile spasms has been written. This multi-authored book comes at a time when the application of new techniques and new therapeutic approaches to the problem of infantile spasms has resulted in significant advances in our understanding …
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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