DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for complement factor I deficiency — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleComplement factor I deficiency maps to a 5-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 complement factor i deficiency 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
fibrinogen alpha chain (FGA) — FGA 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 galdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3GHG · 2.9 Å · ligand beta-D-galactopyranose (GAL). Experimental structure, not a prediction.
What the evidence adds up to
Complement factor I deficiency is a rare complement deficiency state. The complement system comprises plasma and membrane proteins that influence inflammatory response, immune modulation, and host defence. Complement activation proceeds through classical and alternative pathways that converge at C3. Deficiency states are associated with predictable defects in complement-dependent functions and are most prevalent in patients with certain rheumatologic and infectious diseases. Complement appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies.
In autoimmune immune complex disease, the effector side appears to be at fault, and it may be advisable to treat asymptomatic patients with deficiencies of early complement pathway components before they develop disease, though safe and effective methods of doing so are not yet available. Excessive activation and deficiency of complement components or regulators can lead to life-threatening conditions. Complement-targeted therapies are under investigation.
In a 2025 study of anal squamous cell carcinoma patients (n=40), chemoradiotherapy decreased levels of most complement analytes measured, with intact C2, intact C3, intact C5, C3a, C5a, Ba, Bb, SC5b9, Factor D, Factor H, Factor I, and Factor P decreasing three months after treatment specifically in patients achieving complete responses (all p<0.05). The treatment failure group showed changes indicative of persistent alternative complement pathway activation, with a less pronounced decline following chemoradiotherapy compared to responders. Patients in the treatment failure group had elevated baseline levels of intact C2 and Factor D compared to those achieving complete response (both p<0.03). These findings suggest dysregulation of the complement system, particularly involving the alternative pathway, may be more prevalent in patients with a poor treatment response.
In a 2025 mouse model of C3 glomerulopathy, a moss-produced analog of human factor H (CPV-104) was tested in factor H-deficient mice. Using a protocol for sustained depletion of CD20+ B-cells and CD4+ T-cells to prevent antibody formation, repeated CPV-104 administration was able to lastingly resolve C3 deposits. This offers additional rationale for clinical testing of CPV-104 in human C3G patients. What remains missing for complement factor I deficiency specifically is dedicated clinical trial data, funding for drug development, and patient stratification strategies to identify who might benefit from complement-targeted therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Lara D. Veeken · 1993 · 41 citations
COMPLEMENT DEFICIENCY AND DISEASE
AbstractJournal Article COMPLEMENT DEFICIENCY AND DISEASE Get access MARK J. WALPORT MARK J. WALPORT Rheumotology Unit, Hammersmith HospitalDu Cane Road, London W12 0NN Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 32, Issue 4, April 1993, Pages 269–273, https://doi.org/10.1093/rheumatology/32.4.269 Published: 01 April 1993 Article history Accepted: 01 December 1992 Published: 01 April 1993
Infectious diseases associated with complement deficiencies.
AbstractThe complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement-mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies.
Chemical immunology/Fortschritte der Allergielehre/Progress in allergy/Chemical immunology and allergy · 1990 · 13 citations
Complement Deficiency and the Pathogenesis of Autoimmune Immune Complex Disease
AbstractIn the case of the autoimmune immune complex disease it is, however, apparently the effector side that is at fault and this does suggest that it may be advisable to treat asymptomatic patients with deficiencies of the early components of the complement pathway before they develop disease and perhaps to try to avoid prolonged complement depression occurring in disease although it must be confessed that safe and effective methods of so doing are not yet available
LaboratoriumsMedizin · 2012 · 5 citations · open access
Modern complement analysis: indications, methods and outlook1),2)
AbstractAbstract Complement is one of the key systems of innate immunity and homeostasis. Its excessive activation and also a deficiency of complement components or regulators can lead to life-threatening conditions. This review aims to provide the basic knowledge that clinicians need in order to understand complement-related diseases. Moreover, it shows possible indications and interpretations of a complement analysis and explains the rationale behind complement-targeted therapies.
Radiotherapy and Oncology · 2025 · 0 citations · open access
Systemic complement protein levels as biomarkers of chemoradiotherapy response in anal squamous cell carcinoma
AbstractBACKGROUND: Identification of easily measurable biomarkers that are able to predict locoregional failure or disease progression following chemoradiotherapy (CRT) would enable more personalised cancer management. Anal squamous cell cancer (ASCC) is the most common type of anal cancer, accounting for approximately 90% of all cases. While CRT is the standard of care for most locally advanced anal cancers, treatment failure occurs in up to 30% of patients. However, it is currently difficult to predict which patients will fail to respond to treatment, highlighting the need for predictive biomarkers. This study aims to assess whether plasma levels of complement proteins can serve as potential biomarkers of treatment response. MATERIALS AND METHODS: Serial peripheral blood samples from ASCC patients (n = 40) were collected before, during, and after CRT, alongside 6-month clinical and radiological outcomes. Using multiplex ELISA-based technology, we assessed levels of 14 complement proteins at baseline, during CRT, and 3 months post-CRT. Additionally, the same technology was used to compare levels of complement analytes in ASCC and in age- and sex-matched patients without a cancer diagnosis. RESULTS: Our data indicate that CRT decreases levels of most complement analytes measured, with intact C2, intact C3, intact C5, C3a, C5a, Ba, Bb, SC5b9, Factor D, Factor H, Factor I, and Factor P decreasing 3 months after treatment specifically in those patients achieving complete responses (all p < 0.05). Moreover, the treatment failure group showed changes indicative of persistent alternative complement pathway activation, with a less pronounced decline following CRT compared to responders. Furthermore, intact C2 and intact C5 levels were significantly higher in ASCC patients compared to age- and sex-matched patients without a cancer diagnosis (both p < 0.005). In contrast, C3a and C4a were expressed at higher levels in patients without cancer diagnosis compared to ASCC patients (both p < 0.02). Importantly, patients in the treatment failure group had elevated baseline (pre-treatment) levels of intact C2 and Factor D compared to those achieving complete response (both p < 0.03). CONCLUSIONS: These findings suggest that dysregulation of the complement system, particularly involving the alternative pathway, may be more prevalent in patients with a poor treatment response. Intact C2 and Factor D may represent potential markers of treatment failure.
Data Sheet 1_Effective long-term treatment with moss-produced factor H by overcoming the antibody response in a mouse model of C3G.docx
AbstractComplement-associated disorders are caused by the dysregulation and disbalance of the complement system, especially excessive activation. Most drugs that target the complement system are designed to inhibit the complement pathway at either the proximal or terminal levels. The use of a natural complement regulator such as factor H (FH) could provide a superior treatment option by restoring balance to an overactive complement system. We recently reported the moss-based production of an analog of human FH with an optimized glycan profile (CPV-104), which showed in vitro and in vivo characteristics comparable to its human counterpart. Here, we follow up our previous work, focusing in more detail on the time course and long-term efficacy of CPV-104 treatment in FH-deficient (FH<sup>–/–</sup>) mice. The analysis of long-term treatment effects following multiple injections of human FH into mice was previously hindered by the immune response, so we developed a protocol for the sustained depletion of CD20<sup>+</sup> B-cells and CD4<sup>+</sup> T-cells, preventing antibody formation without influencing the C3G phenotype. Using this dual-depletion method, we were able to complete dosing interval experiments in FH<sup>–/–</sup> mice, administering up to three injections of CPV-104 at different intervals. Repeated CPV-104 administration was able to lastingly resolve C3 deposits, offering additional rationale for the clinical testing of CPV-104 in human C3G patients. Moreover, our novel dual-depletion method has the potential for adaptation to different mouse models, allowing the testing of multiple doses of other therapeutic proteins.
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.
