DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for Cytomegalovirus Retinitis — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCytomegalovirus Retinitis maps to a 2-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 cytomegalovirus retinitis 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
colony stimulating factor 2 receptor subunit alpha (CSF2RA) — CSF2RA 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4NKQ · 3.301 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In 22 patients with AIDS and cytomegalovirus retinitis (32 affected eyes), intravitreous cidofovir injections of 20 micrograms given every 5 to 6 weeks produced healing in 100% of eyes with active retinitis (95% CI, 87% to 100%). Mean follow-up was 15.3 weeks. Two episodes of progression occurred in two eyes (6%) from one patient with clinically resistant retinitis. Retinal detachment developed in 3% of eyes. Mild iritis followed 14% of injections that were preceded by oral probenecid prophylaxis. One eye developed irreversible, visually significant hypotonia. No patient received systemic anticytomegalovirus therapy during the study.
In nine patients whose retinitis had progressed despite extended single-drug induction or alternating therapy with ganciclovir or foscarnet, combination intravenous ganciclovir (5 mg/kg every 12 hours) and foscarnet (60 mg/kg every 8 hours) was given. Complete healing occurred in 12 of 14 eyes; partial healing with decreased border activity and cessation of border advancement occurred in the other two. Two of the nine patients stopped combination therapy because of dissatisfaction with the time commitment. No significant medical toxic effects required cessation of therapy.
A prospective study of 108 patients with newly diagnosed cytomegalovirus retinitis found that 80.6% had a positive blood or urine culture for cytomegalovirus at diagnosis. A positive blood culture at diagnosis was associated with increased mortality (odds ratio 1.91, P = 0.012). During follow-up, approximately 20% of cultures remained positive, and a positive blood or urine culture during follow-up correlated with development of retinitis in the contralateral eye in patients with unilateral disease at diagnosis (odds ratio 5.74, P = 0.001). A 1981 letter notes that spontaneous healing with no residual disease had been described, and that adenine arabinoside had been used in the largest reported experience at that time.
What is still missing is a randomised controlled trial comparing intravitreous cidofovir directly with other local or systemic therapies, and long-term safety data beyond 44 weeks. The combination ganciclovir-foscarnet regimen has not been tested in a larger, controlled study, and its optimal dosing and duration remain undefined. The prognostic value of blood cultures has not been translated into a validated strategy for pre-emptive treatment or patient stratification. No trial has addressed whether these findings apply to patients who are not on highly active antiretroviral therapy, which was not yet standard in the 1990s.
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 Internal Medicine · 1996 · 55 citations
Treatment of Cytomegalovirus Retinitis with Intravitreous Cidofovir in Patients with AIDS: A Preliminary Report
AbstractBACKGROUND: Cytomegalovirus retinitis remains a major cause of illness in patients with the acquired immunodeficiency syndrome (AIDS), and existing therapies for this condition are relatively ineffective and toxic. OBJECTIVE: To evaluate the efficacy of intravitreous cidofovir injections alone for initial and maintenance therapy for cytomegalovirus retinitis. DESIGN: Prospective, nonrandomized, consecutive case series. SETTING: University ophthalmology referral clinic. PATIENTS: 22 patients with AIDS and cytomegalovirus retinitis. In 15 of 32 affected eyes, intravitreous cidofovir was administered as the initial treatment for cytomegalovirus retinitis (group A); 17 eyes had previously been treated with intravenous therapy (group B). INTERVENTION: All eyes were intravitreously injected with 20 micrograms of cidofovir at 5- to 6-week intervals. No patient in either group received systemic anticytomegalovirus therapy at any time during the study period. MEASUREMENTS: Healing of retinitis was defined as resolution of retinal opacification and cessation of border progression. Progression, the primary end point, was defined as 750 microns of border progression or development of a new lesion. RESULTS: The mean duration of follow-up was 15.3 weeks (range, 5 to 44 weeks). Of the eyes with active retinitis, 100% (95% CI, 87% to 100%) healed in response to the initial injection. In two eyes (6%; CI, 0% to 15%), two episodes of retinitis progression occurred (one in each eye). Both of these eyes were in a patient with clinically resistant retinitis. In 3% of eyes (CI, 0% to 9%), the retina became detached. Mild iritis developed after 14% of the injections that had been preceded by prophylaxis with oral probenecid. Irreversible, visually significant hypotonia developed in one eye. CONCLUSION: Treatment and subsequent maintenance of cytomegalovirus retinitis with 20 micrograms of intravitreously injected cidofovir, given at 5- to 6-week intervals, is safe and highly effective.
Combination Ganciclovir and Foscarnet in the Treatment of Clinically Resistant Cytomegalovirus Retinitis in Patients With Acquired Immunodeficiency Syndrome
AbstractOBJECTIVE: To assess the clinical response and patient tolerance to daily infusions of both ganciclovir sodium and foscarnet sodium for the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. DESIGN AND PATIENTS: Nine patients with clinically resistant cytomegalovirus retinitis who had shown progression of retinitis despite extended intravenous induction single-drug therapy or alternating therapy with induction doses of ganciclovir or foscarnet at 6 weeks were subsequently treated with a combination of ganciclovir and foscarnet. The dosing regimen for induction combination therapy was ganciclovir at 5 mg/kg every 12 hours and foscarnet at 60 mg/kg every 8 hours. Maintenance combination therapy was ganciclovir at 5 mg/kg every 12 to 24 hours and foscarnet at 90 to 120 mg/kg every day. Patients were observed closely for signs of a toxic effect or intolerance to the drug regimen. RESULTS: All patients exhibited a favorable response to combination therapy, with complete healing of retinitis in 12 of 14 eyes and partial healing of retinitis with decreased border activity and a cessation of border advancement in two of 14 eyes. Two of the nine patients stopped receiving combination therapy before completion of the study owing to their dissatisfaction with the time commitment. The regimen was otherwise well tolerated, with no significant medical toxic effects attributable to the drugs requiring cessation of therapy. CONCLUSIONS: Combination anticytomegalovirus therapy should be considered in those patients who have shown a poor clinical response to sustained single-drug induction therapy and alternating drug therapy. As survival time for patients with cytomegalovirus retinitis continues to improve, clinical resistance may become more common. Further work to delineate the optimal dosing and indications for combination therapy will be important.
American Journal of Ophthalmology · 1998 · 23 citations · open access
Cytomegalovirus retinitis and viral resistance: 3. Culture results
AbstractPURPOSE: To evaluate the relationship between blood and urine cultures for cytomegalovirus and clinical outcomes in patients with cytomegalovirus retinitis. METHODS: Prospective epidemiologic study of 108 patients with newly diagnosed cytomegalovirus retinitis. Blood and urine were cultured for cytomegalovirus at diagnosis of retinitis, at 1 month and 3 months after diagnosis, and every 3 months thereafter. RESULTS: Of the patients, 80.6% were found to have either a positive blood culture or urine culture for cytomegalovirus at the time of diagnosis of retinitis, and a positive blood culture at diagnosis was associated with an increased mortality (odds ratio = 1.91, P = .012). Follow-up cultures were positive in approximately 20% of patients, and the rate was constant over time. The development of a positive blood or urine culture during follow-up correlated with the occurrence of cytomegalovirus retinitis in the contralateral eye in those patients with unilateral disease at diagnosis (odds ratio = 5.74, P = .001). CONCLUSIONS: Patients with cytomegalovirus retinitis and positive blood cultures for cytomegalovirus have a poorer prognosis.
AbstractLetters and Corrections1 March 1981Cytomegalovirus RetinitisMARK B. MOELLER, M.D., JOHN D. HAMILTON, M.D.MARK B. MOELLER, M.D.Search for more papers by this author, JOHN D. HAMILTON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-3-414_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: With their review of cytomegalovirus (CMV) retinitis, Pollard and associates have made a significant contribution (1). Their 14 new cases represent a 45% increase in the number of cases appearing in the literature. Their description of spontaneous healing with no residual evidence of disease broadens the spectrum of a disease previously characterized by progressive retinitis culminating in permanent deficits in visual acuity. Furthermore, their use of adenine arabinoside to treat CMV retinitis is the largest experience reported to date.The authors are to be congratulated for their contribution to our knowledge of CMV retinitis; however, critical examination...References1. POLLARDEGBERTGALLAGHERMERIGAN RPJT. Cytomegalovirus retinitis in immunosuppressed hosts: I. Natural history and effects of treatment with adenine arabinoside. Ann Intern Med. 1980;93:655-64. LinkGoogle Scholar2. CH'IENCANNONWHITLEY LNR. Effect of adenine arabinoside on cytomegalovirus infections. J Infect Dis. 1974;130:32-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Duke University Medical Center Durham, NC 27710 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByA Case of Atopic Dermatitis Successfully Treated with Daiseiryuto 1 March 1981Volume 94, Issue 3Page: 414-414KeywordsAdenineCytomegalovirus infectionRetinitisVisual acuity Issue Published: 1 March 1981 PDF DownloadLoading ...
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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