DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for pulmonary tuberculosis — screening already-approved drugs against its 16-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePulmonary tuberculosis maps to a 16-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 pulmonary tuberculosis 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
adenosine deaminase (ADA) — ADA 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 2r,3s,5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3IAR · 1.52 Å · ligand (2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-tetrahydro-2-(hydroxymethyl)furan-3-ol (3D1). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 study in guinea pigs tested a mutant of Mycobacterium tuberculosis (MtbΔmms) that lacked three phosphatase genes. The mutant was highly attenuated in THP-1 macrophages, and no bacilli were recovered from the lungs or spleens of guinea pigs 10 weeks after inoculation. When used as a vaccine, MtbΔmms produced a significantly reduced bacterial load in the lungs compared to unvaccinated animals at 4 weeks after challenge, and at 12 weeks the protection in the lungs was more sustainable and superior to BCG vaccination. However, the mutant did not control haematogenous spread: the splenic bacillary load was not significantly different between vaccinated and sham-immunised animals. The lipid profiles of the mutant and wild-type M. tuberculosis were identical, so the phenotype was attributed to the loss of the phosphatase genes.
A 2015 study in 60 patients with destructive multidrug-resistant pulmonary tuberculosis added an immunomodulator, glutamyl-cysteinyl-glycine disodium (GCGD), to standard chemotherapy in 30 patients and compared them to 30 patients receiving standard chemotherapy alone. The authors reported that the addition of GCGD increased treatment effectiveness by 33.3%. No further details on the definition of effectiveness, the specific outcomes, or the duration of follow-up were provided in the abstract.
Surgical treatment for pulmonary tuberculosis has been used for decades. A 2009 retrospective review of 33 patients aged 18 to 73 who underwent lung resection reported that the reasons for surgery were haemoptysis (15 patients), lung destruction (9 patients), and active multiresistant disease (9 patients). No patient died in the postoperative period, but complications included empyema (n=5), pneumothorax (n=2), bronchopleural fistula (n=2), and haemothorax (n=2). At six months of follow-up, six of the nine patients with active tuberculosis had negative sputum smears. Two of these nine patients died, one from respiratory failure and one from an unrelated cause; both had negative smears at the time of death. A 1950 report described pneumonectomy in four children aged 3 to 13 years for pulmonary tuberculosis, noting that the operation in children presents problems not encountered in adults.
Earlier reviews from 1928, 1954, and 1988 describe the evolution of treatment from rest and collapse therapy through the introduction of antibiotics, chemotherapeutic drugs, and resectional surgery, and later to short-course chemotherapy of 6 or 9 months. A 2014 clinical study noted that the treatment of tuberculosis patients who also have lung cancer is limited to chemotherapy, surgery, and radiotherapy, and that the two diseases may be linked through immune abnormalities, chronic inflammation, and scar repair.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2013 · 40 citations · open access
Secretory Phosphatases Deficient Mutant of Mycobacterium tuberculosis Imparts Protection at the Primary Site of Infection in Guinea Pigs
AbstractBACKGROUND: The failure of Mycobacterium bovis Bacille Calmette-Guérin to impart satisfactory protection against adult pulmonary tuberculosis has necessitated the development of more effective TB vaccines. The assumption that the vaccine strain should be antigenically as similar as possible to the disease causing pathogen has led to the evaluation of M.tuberculosis mutants as candidate tuberculosis vaccines. METHODS/PRINCIPAL FINDINGS: In this study, we have generated a mutant of M.tuberculosis (Mtb∆mms) by disrupting 3 virulence genes encoding a mycobacterial secretory acid phosphatase (sapM) and two phosphotyrosine protein phosphatases (mptpA and mptpB) and have evaluated its protective efficacy in guinea pigs. We observed that Mtb∆mms was highly attenuated in THP-1 macrophages. Moreover, no bacilli were recovered from the lungs and spleens of guinea pigs after 10 weeks of Mtb∆mms inoculation, although, initially, the mutant exhibited some growth in the spleens. Subsequently, when Mtb∆mms was evaluated for its protective efficacy, we observed that similar to BCG vaccination, Mtb∆mms exhibited a significantly reduced CFU in the lungs of guinea pigs when compared with the unvaccinated animals at 4 weeks after challenge. In addition, our observations at 12 weeks post challenge demonstrated that Mtb∆mms exhibited a more sustainable and superior protection in lungs as compared to BCG. However, the mutant failed to control the hematogenous spread as the splenic bacillary load between Mtb∆mms vaccinated and sham immunized animals was not significantly different. The gross pathological observations and histopathological observations corroborated the bacterial findings. Inspite of disruption of phosphatase genes in MtbΔmms, the lipid profiles of M.tuberculosis and MtbΔmms were identical indicating thereby that the phenotype of the mutant was ascribed to the loss of phosphatase genes and the influence was not related to any alteration in the lipid composition. CONCLUSIONS/SIGNIFICANCE: This study highlights the importance of M.tuberculosis mutants in imparting protection against pulmonary TB.
Archives of Pediatrics and Adolescent Medicine · 1950 · 7 citations
EXCISIONAL SURGICAL TREATMENT OF PULMONARY TUBERCULOSIS IN CHILDREN
AbstractPNEUMONECTOMY, or resection of the diseased lung, in the treatment of pulmonary tuberculosis in adults is now an accepted procedure, although indications for its employment remain controversial. While pneumonectomies have been performed in children, mainly for bronchiectasis, we were unable to find, in a review of the literature, cases of pulmonary tuberculosis treated in this manner. There are, however, brief references to lobectomies in the treatment of this disease in persons in the growing age period, with apparent success.<sup>1</sup> As the disease in children usually does not progress to the stage that makes this form of therapy necessary, reports can be presented on only 4 patients in whom pneumonectomy was performed since November 1946 for pulmonary tuberculosis. The children ranged in age from 3 to 13 years at the time of operation. The operation in children presents problems not encountered in adults. Obliteration of the residual "dead space" created
Revista médica de Chile · 2009 · 3 citations · open access
Cirugía pulmonar en tuberculosis
AbstractBACKGROUND: Surgical treatment for pulmonary tuberculosis is mainly limited to the management of sequelae such as bronchiectasis, hemoptysis and brochopleural fistulae. AIM: To review the data of patients who underwent surgical treatment for pulmonary tuberculosis. MATERIAL AND METHODS: Retrospective review of 33 patients aged 18 to 73 years (24 males) who underwent lung resection surgery for the management of pulmonary tuberculosis. Follow-up data were obtained from outpatient visit records and registries of the national tuberculosis program. RESULTS: The reasons to perform surgery were the following: fifteen for hemoptysis, nine for lung destruction and nine for an active and multiresistant disease. No patient died in the postoperative period. The morbidity observed included empyema (n =5), pneumothorax (n =2), bronchopleural fistula (n =2) and hemothorax (n =2). At six months of follow up, six of the nine patients with active tuberculosis had negative acid-fast bacilli on sputum smear. Two of these patients died, one due to respiratory failure and another by an unrelated cause. Both dead patients had negative acid-fast bacilli on sputum smear. CONCLUSIONS: Surgery in pulmonary tuberculosis has a high rate of complications but may be useful in selected patients.
Drug and Therapeutics Bulletin · 1988 · 3 citations
Chemotherapy of pulmonary tuberculosis in britain
AbstractTreatment of pulmonary tuberculosis has changed much since we last discussed it 12 years ago 1 : PAS has been replaced by more effective and better tolerated drugs, and short-course (6 or 9 months) chemotherapy is now the first choice. Attempts are being made to shorten the treatment further. Shorter treatment is easier for patients, uses fewer medical resources and costs less. This article reviews the drug regimens that are currently recommended for treating pulmonary tuberculosis.
The Evolution of the Modern Treatment of Pulmonary Tuberculosis
AbstractArticle1 June 1928The Evolution of the Modern Treatment of Pulmonary TuberculosisCHARLES L. MINORCHARLES L. MINORSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-12-996 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the treatment of disease there is always occurring an ebb and flow in the tide of medical opinion and out of this is finally evolved the accepted standard of practice.I would ask your attention today to a resume of this evolution insofar as it affects the treatment of Pulmonary Tuberculosis.Much of the therapeutic teaching of any period is discarded in thirty or forty years as not standing the test of experience or not having a reliable scientific foundation and much of our present day treatment we may be sure will go on the scrap heap in the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Asheville, N. C.*Presented before the American College of Physicians, March 6, 1928, New Orleans, La. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1928Volume 1, Issue 12Page: 996-1003KeywordsPulmonary diseases ePublished: 1 December 2008 Issue Published: 1 June 1928 PDF downloadLoading ...
Current issues in pharmacy and medicine science and practice · 2015 · 1 citations · open access
Effectiveness of using Glutamyl-cysteinyl-glycine disodium immunomodulator in patients with destructive multidrug-resistant tuberculosis of lungs
AbstractImportance of the problem: treatment efficiency improving in patients with multidrug-resistant destructive pulmonary tuberculosis (MDR).Aim. To study the complex treatment effectiveness in patients with destructive MDR with implementation of Glutamyl-cysteinyl-glycine disodium (GCGD) immunomodulator.Methods and results. On the basis of standard chemotherapy course main treatment effectiveness parameters have been estimated of 30 patients who were treated with implementation of GCGD on the basis of standard chemotherapy course and 30 patients who were treated with standard chemotherapy course alone.Conclusion. Complex treatment of patients with destructive MDR with implementation of GCGD immunomodulator on the basis of standard chemotherapy course for immunity state correction allows to increase effectiveness of treatment by 33,3%.
Current Concepts in the Treatment of Pulmonary Tuberculosis
AbstractToday we are armed with more and better weapons against tuberculosis than at any time in the past. Time-honored rest and collapse therapy have been supplemented with antibiotics, chemotherapeutic drugs, and resectional surgery. This article presents an evaluation of their relative merits in the therapy of pulmonary tuberculosis. Current fundamental concepts are emphasized and a program of therapy is suggested.
Clinical study on the relationship between pulmonary tuberculosis and lung cancer
AbstractThe pathogenesis of pulmonary tuberculosis involves inflammatory mediators reaction,and the pathogenesis of lung cancer is complex,involving multiple genes and molecules.The lung cancer has some relevance with pulmonary tuberculosis in terms of immune abnormalities,antituberculosis drugs,scar repair,chronic inflammation and tuberculin virulence.The treatment of tuberculosis patients with lung cancer is limited to chemotherapy,surgery and radiotherapy.
Key words:
Lung neoplasms ; Tuberculosis, pulmonary; Oncogenes; Genes, tumor suppressor
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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