DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for scrapie — 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 moduleScrapie 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 scrapie 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
ATP binding cassette subfamily B member 6 (LAN blood group) (ABCB6) — ABCB6 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 y01drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9DBQ · 2.9 Å · ligand CHOLESTEROL HEMISUCCINATE (Y01). Experimental structure, not a prediction.
What the evidence adds up to
The 2003 review summarises the epidemiology of scrapie, covering geographical distribution, pathogenesis, transmission, genetic influence, and flock dynamics, along with risk factors for spread within and between flocks. It states that the science may assist in providing a foundation for prevention and control programmes, and gives examples of national scrapie programmes.
A 2014 quantitative risk assessment modelled the safety of carcase storage systems on scrapie-infected farms. For an example farm with classical scrapie, a mean of 10³·⁶ Ovine Oral ID₅₀ was estimated to accumulate annually. The degradation of any prions present may range from insignificant to a magnitude of one or two logs over several months of storage. The likely partitioning of remaining prion into the sludge phase would necessitate safe operation and removal of materials. If complete mixing could be assumed, the average concentrations of infectivity were estimated to be slightly lower than that measured in placenta from infected sheep at lambing.
A 2009 study investigated whether the number of scrapie cases in a holding is proportional to holding size, using surveillance data on classical scrapie in Great Britain. No evidence for proportionality was found; the relationship followed a curved line that increased for small holdings up to a maximum and then declined. Estimators based on the proportionality model returned very different and unreasonable estimates for the affected holding population size. The authors concluded that reporting artefacts and speculative biological effects are hypothesised as underlying causes of the curved relationship, and that the lack of adjustment for these artefacts might well render current disease control strategies ineffective.
What is still missing is a clear biological explanation for the non-proportional relationship between holding size and case count, and any validated adjustment for reporting artefacts. No trial design or patient stratification exists because scrapie is an animal disease with no human treatment being tested in these abstracts. The studies also lack direct funding for intervention trials or for resolving the degradation kinetics of prions in farm waste.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Revue Scientifique et Technique de l OIE · 2003 · 186 citations
The epidemiology of scrapie
AbstractThis review provides an update on the epidemiology of scrapie. The authors provide historical and recent information regarding the determination of geographical distribution, pathogenesis, transmission, genetic influence and the dynamics of scrapie within a flock. Also described are the risk factors associated with the disease and its spread within and between flocks. The current science may assist in providing a foundation on which prevention and control programmes may be based. Some examples of current national scrapie programmes are summarised.
Reversible Chemical Modification of the Scrapie Agent
AbstractThe scrapie agent causes a degenerative nervous system disease in sheep and goats. Studies with extensively purified preparations demonstrated that the agent contains a protein that is required for infectivity. Chemical modification of the scrapie agent by diethyl pyrocarbonate reduced the titer 1000-fold. Exposure of the inactivated agent to hydroxylamine, a strong nucleophile, resulted in complete restoration of infectivity. Presumably, nucleophilic residues within a scrapie agent protein undergo carbethoxylation on reaction with diethyl pyrocarbonate, and subsequent addition of hydroxylamine displaces these carbethoxy groups.
Journal of Applied Microbiology · 2014 · 5 citations
A quantitative risk assessment for the safety of carcase storage systems for scrapie infected farms
AbstractAIMS: To determine the risk associated with the use of carcase storage vessels on a scrapie infected farm. METHODS AND RESULTS: A stochastic quantitative risk assessment was developed to determine the rate of accumulation and fate of scrapie in a novel low-input storage system. For an example farm infected with classical scrapie, a mean of 10(3·6) Ovine Oral ID50 s was estimated to accumulate annually. Research indicates that the degradation of any prions present may range from insignificant to a magnitude of one or two logs over several months of storage. CONCLUSIONS: For infected farms, the likely partitioning of remaining prion into the sludge phase would necessitate the safe operation and removal of resulting materials from these systems. If complete mixing could be assumed, on average, the concentrations of infectivity are estimated to be slightly lower than that measured in placenta from infected sheep at lambing. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first quantitative assessment of the scrapie risk associated with fallen stock on farm and provides guidance to policy makers on the safety of one type of storage system and the relative risk when compared to other materials present on an infected farm.
BMC Veterinary Research · 2009 · 2 citations · open access
On the question of proportionality of the count of observed Scrapie cases and the size of holding
AbstractBACKGROUND: The present paper investigates the question of a suitable basic model for the number of scrapie cases in a holding and applications of this knowledge to the estimation of scrapie-affected holding population sizes and adequacy of control measures within holding. Is the number of scrapie cases proportional to the size of the holding in which case it should be incorporated into the parameter of the error distribution for the scrapie counts? Or, is there a different - potentially more complex - relationship between case count and holding size in which case the information about the size of the holding should be better incorporated as a covariate in the modeling? METHODS: We show that this question can be appropriately addressed via a simple zero-truncated Poisson model in which the hypothesis of proportionality enters as a special offset-model. Model comparisons can be achieved by means of likelihood ratio testing. The procedure is illustrated by means of surveillance data on classical scrapie in Great Britain. Furthermore, the model with the best fit is used to estimate the size of the scrapie-affected holding population in Great Britain by means of two capture-recapture estimators: the Poisson estimator and the generalized Zelterman estimator. RESULTS: No evidence could be found for the hypothesis of proportionality. In fact, there is some evidence that this relationship follows a curved line which increases for small holdings up to a maximum after which it declines again. Furthermore, it is pointed out how crucial the correct model choice is when applied to capture-recapture estimation on the basis of zero-truncated Poisson models as well as on the basis of the generalized Zelterman estimator. Estimators based on the proportionality model return very different and unreasonable estimates for the population sizes. CONCLUSION: Our results stress the importance of an adequate modelling approach to the association between holding size and the number of cases of classical scrapie within holding. Reporting artefacts and speculative biological effects are hypothesized as the underlying causes of the observed curved relationship. The lack of adjustment for these artefacts might well render ineffective the current strategies for the control of the 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.
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.
