DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for osteomyelitis — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleOsteomyelitis maps to a 31-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 osteomyelitis 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
phosphoglycerate dehydrogenase (PHGDH) — PHGDH 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6RJ3 · 1.42 Å · ligand 4-[(1~{R})-1-[(2-methyl-5-phenyl-pyrazol-3-yl)carbonylamino]ethyl]benzoic acid (K58). Experimental structure, not a prediction.
What the evidence adds up to
In a 2019 study, pyroptosis-associated proteins NLRP3, Caspase1 and GSDMD were found at significantly higher levels in infectious bone fragments from patients with osteomyelitis than in uninfected bone. In a mouse model of Staphylococcus aureus-induced osteomyelitis, the same proteins were elevated. Inhibitors of these proteins reduced pyroptosis both in cell culture and in mice. The inhibition also restored bone-forming activity, reduced abnormal osteoclast activation in vitro, and reversed bone injury in the mouse model. The study identifies pyroptosis as a pathway in osteomyelitis and suggests that blocking it might be a treatment target. No human trial of such inhibitors is reported.
A 2019 review of chronic osteomyelitis literature summarises diagnostic and treatment options but does not present new clinical data. A 1945 paper on penicillin treatment for chronic osteomyelitis notes that despite successes with penicillin in other infections, results in chronic osteomyelitis were disappointing. The author attributes this to the nature of the chronic lesion and the need to understand its pathology for rational therapy.
What is missing: no clinical trial of pyroptosis inhibitors in human osteomyelitis has been conducted. The 1945 observation that chronic osteomyelitis resists even potent antibiotics remains relevant. Funding for a properly stratified human trial, with clear endpoints for bone healing and infection clearance, is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Translational Medicine · 2019 · 68 citations · open access
Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis
AbstractBackground: Osteomyelitis is a severe bone infection and typically leads to progressive bone resorption, destruction and dysfunction. Pyroptosis is a form of programmed cell death involved in various infectious diseases. However, the identification of pyroptosis and the role it plays in osteomyelitis remains to be clarified. In this study, we investigated the expression of pyroptosis-associated proteins in osteomyelitis and the effects of inhibiting pyroptosis on S. aureus-induced osteomyelitis both in vitro and in vivo. Methods: The expression of pyroptosis-associated protein—NLRP3 (NLR Family Pyrin Domain Containing 3), Caspase1 and GSDMD (GasderminD) were examined in murine and human infectious bone fragments by western blot. Bone destruction was evaluated by microcomputed tomography (µCT). The concentration of inflammatory factors was tested by Enzyme linked Immunosorbent Assay (ELISA). The expression of pyroptosis-associated gene was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Results: The expression of pyroptosis-associated proteins in infectious bone fragments from patients with osteomyelitis was significantly higher than uninfected bone. Additionally, in S. aureus-induced murine osteomyelitis model, higher expression of pyroptosis-associated proteins was noticed. Furthermore, the inhibitors of pyroptosis-associated proteins alleviated S. aureus-induced pyroptosis both in vivo and in vitro. More importantly, the inhibition of pyroptosis restored the bone formative property, attenuated the aberrant activation of osteoclast in vitro and reversed bone injury in vivo. Conclusions: Our study identified pyroptosis as a key pathway in osteomyelitis and elaborated that the inhibition of pyroptosis could attenuate S. aureus-induced bone destruction in osteomyelitis, providing a potential treatment target to osteomyelitis.
Research Progress on Diagnosis and Treatment of Chronic Osteomyelitis
AbstractWe review the representatives literatures on chronic osteomyelitis, sum up the new insights in recent years into diagnostic options and treatment regimens, analyze the advantages and disadvantages of various diagnostic approaches and treatment strategies, and propose areas of interest to make current diagnostic and treatment strategies more specific.
PENICILLIN IN THE TREATMENT OF CHRONIC OSTEOMYELITIS
AbstractThe history of the treatment of chronic osteomyelitis is replete with many rebuffs to the suffering victims, despite the application of many new procedures and drugs and serums which have been developed in recent decades. Notwithstanding the fact that these new approaches have produced spectacular results in the treatment of other types of infections, they have been found wanting in the treatment of chronic osteomyelitis. These failures are due to the inherent nature of the chronic osteomyelitic lesion. Many hopes, raised high with the advent of every new therapeutic agent, have met with disappointment due to the lack of appreciation of the differences existing between the chronic osteomyelitic lesion and other lesions and the specialized problems involved in the cure of the disease under consideration Rational therapy can be administered only when the pathologic character of the involvement is appreciated. Briefly, the chronic osteomyelitic lesion presents a diseased bone which
European Journal of Pediatric Surgery · 1982 · 1 citations
Die heutige Therapie der chronischen Osteomyelitis (Osteitis) im Kindesalter
AbstractThe article reports on experience collected in the treatment of chronic osteomyelitis in children. Surgical procedure is described and attention is paid to indication and treatment with gentamycin polymethylmethacrylate chains. In 15 cases treated by the author, primary cure was achieved by this method in 13 children; additional surgical procedure became necessary in two cases.
AbstractIn acute hematogenous osteomyelitis, treatment is directed toward overcoming the generalized infection and controlling the local bone lesion. Use of sulfonamides and penicillin in a program of conservative treatment is discussed; 2 cases of acute osteomyelitis are described in which operative treatment was withheld. Emphasis is placed on the fact that in chronic osteomyelitis there is always a sequestrum or some situation subject to treatment; most such patients with chronic draining sinuses can be healed by a proper surgical approach.
Central Plains Medical Journal · 2013 · 0 citations
Clinical efficacy of acid water on distal lower extremity osteomyelitis
AbstractObjective To evaluate the clinical efficacy of acid water on distal lower extremity chronic osteomyelitis.Methods Between July 2011 and November 2012,11 patients with lots of exudates of chronic osteomyelitis were treated in our hospital.After the focus of infection was debrided completely,they were treated with acid water.As soon as the wound surface was clear and the surface was covered with granulating tissue,the wounds were treaded with secondary directly sutured or closed by skin transplantation.Results The exudates and the area of the wound were both decreased after rinsed and soaked in acid water for 10-25 days,with an average of 19 days.The wound was covered by second suture or flap transplantation.After of followed-up of 6-18 months,all 11 cases of chronic osteomyelitis were healed with no recurrence.Conclusions Application of acid water in treatment of osteomyelitis is effective and feasible,it has low medical cost,with good social and economic benefits,and provides a new option for the treatment of chronic osteomyelitis of the distal limbs.
Key words:
Chronic osteomyelitis ; Acid water; Treatment
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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