DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for scleritis — screening already-approved drugs against its 17-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleScleritis maps to a 17-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 scleritis 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
methylthioadenosine phosphorylase (MTAP) — MTAP 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 2s,3s,4r,5sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5TC6 · 1.48 Å · ligand (2S,3S,4R,5S)-2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-[(propylsulfanyl)methyl]pyrrolidine-3,4-diol (7A6). Experimental structure, not a prediction.
What the evidence adds up to
Ten patients with severe and refractory scleritis were treated with anakinra 100 mg/day subcutaneously in a pilot study. Ninety percent were complete responders over a mean follow-up of 19.4 months. The mean daily corticosteroid dose fell from 18.3 mg to 4.2 mg, and all but one patient stopped concomitant immunosuppressants. Side effects occurred in four patients but did not require drug withdrawal. The authors caution that this was a pilot study.
Three patients with systemic autoimmune disease-associated refractory anterior scleritis were treated with tofacitinib 10 mg/day in a case series. All three achieved complete resolution, with no recurrence during 39 to 78 months of follow-up and no reported adverse effects. Two patients were on tofacitinib monotherapy at last follow-up, and one was on no treatment. The authors call for larger clinical trials. An earlier case series from 2023 also reported tofacitinib use in three patients with refractory scleritis who were recalcitrant or intolerant to conventional therapy.
Subconjunctival rituximab injections at doses of 2.5 to 7.5 mg were given to three patients with severe, active, non-infectious scleritis refractory or intolerant to systemic treatment. Over 8 to 10 months of follow-up, the injections showed minimal to no effect on subjective symptoms, clinical features, or ultrasound images. No serious adverse effects occurred. The authors state that this limited observation is not promising.
A 2010 review notes that large-scale retrospective reviews of standard corticosteroid-sparing systemic therapies have demonstrated only moderate efficacy for any particular immunomodulatory agent, while new data confirmed excellent efficacy and tolerability for subconjunctival corticosteroids. The same review states that local treatment with steroid injections may help reduce side effects from systemic therapy in patients with active scleritis in the absence of active systemic disease, but cautions that results from small retrospective case series should be interpreted with caution. What is still missing are large, randomised controlled trials that can confirm the efficacy of any of these agents, define optimal patient stratification by disease subtype or systemic association, and provide long-term safety data beyond small case series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Ophthalmology · 2005 · 29 citations · open access
Congenital hypertrophy of retinal pigment epithelium: a clinico-pathological case report
Abstractscleritis in appropriately selected patients and that this therapy is not unequivocally associated with the risk of scleral thinning or perforation. Local treatment with steroid injections may help reduce potential side effects from systemic therapy in patients with active scleritis in the absence of active systemic disease. As with all retrospective small case series our results should be interpreted with caution.
Ocular Immunology and Inflammation · 2017 · 25 citations
Anakinra in the Treatment of Patients with Refractory Scleritis: A Pilot Study
AbstractPURPOSE: This study aimed to evaluate the safety and efficacy of anakinra for severe and refractory scleritis. METHODS: Ten patients with severe (i.e. at least 2 ocular relapses per year despite treatment) and refractory [i.e. at least to one disease modifying antirheumatic drugs (DMARDS)] scleritis were treated with anakinra (100 mg/day subcutaneously). Scleritis was associated with inflammatory systemic diseases in 60% of cases. The remission rate defined the primary outcome. RESULTS: Ninety percent of patients were complete responders with a mean follow-up of 19.4 months after starting anakinra. The corticosteroids daily dose decreased from 18.3 ± 4.1 mg to 4.2 ± 4.9 mg, (p < 0.05), at initiation of anakinra and at end of follow-up, respectively. Associated immunosuppressants were stopped in all cases except one. Side effects were observed in 4 patients who did not need anakinra withdrawal. CONCLUSIONS: This pilot study suggests the efficacy of anakinra in patients with refractory scleritis.
Current Opinion in Ophthalmology · 2010 · 25 citations
An update on the cause and treatment of scleritis
AbstractPURPOSE OF REVIEW: To review new clinically relevant data regarding the cause and treatment of scleritis that has been identified over the past 36 months. RECENT FINDINGS: A recently described T-helper cell population, known as Th-17, has been implicated in scleritis. Large-scale, retrospective reviews of standard corticosteroid-sparing systemic therapies, published in the last few years, have demonstrated only moderate efficacy for any particular immunomodulatory agent, whereas new data have confirmed excellent efficacy and tolerability to subconjunctival corticosteroids. SUMMARY: Improved understanding of the immunopathophysiology of scleritis offers hope for future molecule-specific drug design. Data continue to support the use of local steroids as a reasonable therapeutic option for nonnecrotizing, noninfectious anterior scleritis.
Mediterranean Journal of Rheumatology · 2023 · 14 citations · open access
Tofacitinib in Refractory Scleritis: A Case Series
AbstractTofacitinib, a Janus kinase inhibitor, has been recently investigated as a potential therapy for refractory scleritis. Despite treatment with systemic immunosuppressive agents, scleritis is refractory to conventional therapy in a significant number of patients. Hereby, we report the use of tofacitinib as a steroid-sparing immunomodulatory agent in three patients with refractory scleritis who were either recalcitrant or intolerant to conventional therapy.
Klinische Monatsblätter für Augenheilkunde · 2012 · 10 citations
Scleritis after Proton Therapy in Uveal Melanoma
AbstractBACKGROUND: Sclera is a very radioresistant tissue and scleritis after proton therapy has not been described so far. HISTORY AND SIGNS: Four female patients, aged between 31 and 74 years, were treated with proton therapy for uveal melanoma (height range: 2.2 - 3.5 mm), located in the macula, the superior equator and 2 in the ciliary body. All patients had a history of a previous or active inflammatory disease and developed scleritis after radiotherapy. THERAPY AND OUTCOME: Two patients had infectious scleritis and were treated with adequate antibiotic therapy. After systemic corticotherapy, 3 patients recovered completely; the remaining patient was managed with additional immunosuppressive treatment as well as a conjunctival and scleral graft, but has not become pain free yet. CONCLUSION: Scleritis is a possible complication after proton therapy, probably on an ischemic basis, where there is a predisposing factor such as inflammatory systemic disease.
Ocular Immunology and Inflammation · 2024 · 6 citations
Long-Term Outcome of Tofacitinib Treatment for Systemic Autoimmune Disease-Associated Refractory Scleritis
AbstractPURPOSE: To report the long-term outcome of three refractory anterior scleritis cases successfully treated with tofacitinib, a Janus-associated kinase inhibitor. METHODS: Three patients with systemic autoimmune disease-associated anterior scleritis (two with rheumatoid arthritis and one with systemic lupus erythematosus), resistant to conventional immunomodulatory therapy, were subsequently treated with tofacitinib (10 mg/day). RESULTS: Tofacitinib resulted in complete resolution of scleritis in all patients. During the 39-78 months of follow-up, no recurrence of scleritis occurred, and no adverse effects associated with tofacitinib were noted. At the last follow-up, all patients were free of scleritis with two patients receiving tofacitinib monotherapy and one without. CONCLUSION: Tofacitinib can be a safe and effective treatment for noninfectious refractory scleritis, warranting further investigation in large clinical trials.
Ocular Immunology and Inflammation · 2022 · 3 citations
Subconjunctival Rituximab Administration for the Treatment of Scleritis
AbstractPURPOSE: Scleritis is a sight-threatening inflammation, which is commonly accompanied by severe complications. Aggressive systemic immunosuppressive treatment, which is frequently needed, can be associated with serious complications, and might therefore be (temporarily) contraindicated. METHODS: We report on the outcomes of three patients with severe, active, non-infectious scleritis, refractory or intolerant to systemic treatment, who received subconjunctival rituximab (RTX) injections. A dose of 2.5 to 7.5 mg was administered after topical anesthesia, and follow-up varied from 8 to 10 months. RESULTS: Subconjunctival RTX showed minimal to no effect on subjective symptoms, clinical features and/or ultrasound images. No serious adverse effects occurred. CONCLUSION: Further studies are needed to assess the effect of local administration of RTX in scleritis, but our limited observation is not promising.
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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