DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for severe combined immunodeficiency — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSevere combined immunodeficiency maps to a 35-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 severe combined immunodeficiency 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 1994 study of nine HIV-positive patients with squamous-cell carcinoma of the anus reported that seven achieved a complete clinical response after combined radiation and chemotherapy with 5-fluorouracil and mitomycin C. All Stage I/II patients and one of four Stage III patients remained alive with no evidence of disease at a median follow-up of 8 months. However, Grades 3 and 4 skin toxicity occurred in six patients, and Grades 2 and 3 myelosuppression in eight patients. The authors concluded that toxicity was increased compared to non-HIV patients, and that the value of combined modality treatment in AIDS patients or those with advanced disease was questionable.
For severe combined immunodeficiency itself, a 2011 review noted that haematopoietic stem cell transplantation may be curative but that a suitable donor is often unavailable, and even with a matched donor the procedure carries risks of graft-versus-host disease and side effects from myelosuppressive chemotherapy. The review described advances in gene therapy for X-linked SCID and adenosine deaminase-deficient SCID, citing trials in Italy, France, and the United States that showed clinical benefits from transplantation of gene-modified autologous stem cells. No concrete survival or response numbers were given in that summary.
A 2017 review of novel HIV therapy approaches stated that there are approximately 35 million people infected with HIV globally, with an estimated 2 million new infections per year. It noted that antiretroviral therapy has transformed HIV into a chronic and manageable disease and that treated patients are much less likely to transmit infection, but it did not address SCID. A 2002 review of X-linked SCID mentioned that molecular techniques had introduced new treatments into clinical practice but provided no specific outcome data.
What is still missing are large, controlled trials comparing gene therapy directly with standard haematopoietic stem cell transplantation for SCID, with long-term follow-up of immune reconstitution and adverse events. Funding for such trials, reliable methods of patient stratification by genetic subtype, and standardised reporting of toxicity and survival remain absent from the available literature.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diseases of the Colon & Rectum · 1994 · 87 citations
Squamous-cell carcinoma of the anus in HIV-positive patients
AbstractPURPOSE: Patients diagnosed as having anal cancer and human immunodeficiency virus (HIV)-positive disease were evaluated for response to treatment and its associated toxicity. METHODS: We studied nine HIV-positive patients with squamous-cell carcinoma of the anus. Among them, three patients had acquired immunodeficiency syndrome (AIDS). The stage of disease at presentation included: one Stage 0, two Stage I, two Stage II, and four Stage III patients. Seven patients received combined modality treatment, i.e., radiation therapy and chemotherapy, and two patients received radiation therapy alone. The radiation therapy field included the pelvis and a conedown boost. Chemotherapy consisted of two cycles of 5-fluorouracil and mitomycin C. Patients have been followed from 2 to 42 (median, 8) months. RESULTS: Seven patients achieved a complete response clinically. All Stage I/II patients and one of four Stage III patients remain alive and have no evidence of disease. Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer Grades 3 and 4 skin toxicity were noted in six patients, and Grades 2 and 3 myelosuppression were noted in eight patients. The response rates achieved are comparable to the experience in non-HIV patients reported in the literature, but toxicity seems to be increased. CONCLUSION: It would seem reasonable to offer combined modality treatment to early stage, HIV-positive patients with good performance status and a history of minor opportunistic infections. The value of combined modality in AIDS patients and those who present with advanced stages of the disease is questionable.
Science Translational Medicine · 2011 · 21 citations
A Tale of Two SCIDs
AbstractHematopoietic stem cell (HSC) transplantation may be curative for severe combined immunodeficiency (SCID). However, for a majority of infants with SCID a suitable donor is not available, and even with a matched donor, allogeneic HSC transplantation itself carries potential complications such as graft-versus-host disease as well as side effects from myelosuppressive chemotherapy. In the past decade, substantial advances have been made in the transplantation of gene-modified autologous HSCs, especially for two forms of SCID: X-linked SCID (SCID-X1) and adenosine deaminase (ADA)-deficient SCID. Two new reports in this issue of Science Translational Medicine add to the accumulating findings from gene therapy trials in Italy, France, and the United States that show clinical benefits of this alternative treatment.
AbstractThere are approximately 35 million people infected by human immunodeficiency virus (HIV), with an estimated 2 million incident infections annually across the globe. While HIV infection was initially associated with high rates of morbidity and mortality, advances in therapy have transformed it into a chronic and manageable disease. In addition, there is very strong evidence that those on antiretroviral therapy are much less likely to transmit infection to their partners. The success rates for maintaining viral suppression in treated patients has dramatically increased owing to the development of agents that are potent and well tolerated and can often be co-formulated into single pills for simplification. This review will outline advances in treatment over the last several years as well as new strategies that may shift the existing treatment paradigm in the near future.
AbstractSevere combined immunodeficiency is one of the most common causes of primary immunodeficiencies in humans. Molecular biological techniques have allowed new, therapeutically useful treatments for these diseases to be introduced into clinical practice. This review will focus on the molecular basis and new treatments for X-linked severe combined immunodeficiency.
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.
